bicoid: Biological Overview | Evolutionary Homologs | Regulation | Targets of Activity | Protein Interactions | Miscellaneous Interactions: Control of Bicoid mRNA subcellular distribution | Developmental Biology | Effects of Mutation | References

Gene name - bicoid

Synonyms -

Cytological map position - 84A1

Function - transcription factor

Keywords - morphogen, anterior-posterior axis - anterior group

Symbol - bcd

FlyBase ID:FBgn0000166

Genetic map position - 3-[47.5]

Classification - homeodomain

Cellular location - nuclear

NCBI links: Precomputed BLAST | Entrez Gene | UniGene

The maternally transcribed gene bicoid organizes anterior development in Drosophila. Its mRNA remains localized at the anterior tip of the oocyte and later in the early embryonic stages. Maternal bcd transcription is regulated by the maternal transcription factor Serendipity delta. Bicoid mRNA translation is inhibited in the posterior by Nanos (Payre, 1994 and Gavis, 1995).

The protein cannot be detected in oocytes, indicating translation of bicoid is inhibited prior to fertilization. Zygotic translation can be detected shortly after egg deposition, and immediately after fertilization, at the anterior tip of the embryo. As a consequnce of the anterior localization of RNA, a gradient of Bicoid protein becomes established prior to cellularization (Driever, 1988).

Localization of BCD RNA is a multi-step process including an early event taking place in nurse cells requiring Exuperentia and a later event in the oocyte requiring Gurken and involving the cytoskeleton.

Initial stages in localization of BCD mRNA take place in nurse cells, mediated by a cis acting localization signal, (the Bicoid localization element [BLE1]), which is present as part of the 3' untranslated region of Bicoid mRNA. The exuperentia gene product required for Bicoid anterior localization (Berleth, 1988), has been considered to be the BLE binding agent. However, RNA binding activity has not been detected for EXU. Instead, another protein from wild type exu flies has been found associated with BCD RNA . This BCD RNA binding protein has been termed Exu-like (EXL). It is possible that both EXL and EXU interact with BLE (MacDonald, 1995).

BCD ultimately finds its way to the anterior pole of the oocyte as a ribonuclear protein complex. It may also be transported along microtubules in vesicles (Wang, 1994). Zygotic translation of Bicoid RNA ensues rapidly upon fertilization. Transition from maternal to zygotic conditions requires an increase in polyadenylation in the Bicoid messenger RNA. The successful translation of RNA into proteins requires polyadenylation. In this process adenyl residues attach to the 3' end of the Bicoid RNA, contributing to its stability and preparing it for translation. Maternal RNAs must be kept inactive until needed. A major cellular mechanism for the maintenance of inactive mRNA in the oocyte is the lack of adenyl residues (Salles, 1994).

The anterior-posterior gradient of Bicoid plus its partner Hunchback are required to either activate or inhibit transcription of a variety of zygotic genes, including hunchback, gap genes such as empty spiracles, Krüppel and knirps, pair rule genes like even-skipped and runt, and even some homeotic and Polycomb group genes. Thus Bicoid has an essential role in establishing the anterior-posterior axis of Drosophila, its gradient acting to position the transcription of gap and pair rule genes along the anterior-posterior axis.

Bicoid mRNA translation is posttranscriptionally regulated by Nanos protein. It would seem that one requirement for NOS mRNA localization, involving 11 proteins of the posterior group are imposed by the presence of the Nanos response elements in BCD and HB mRNAs (Wharton, 1991).

High Bicoid levels render the terminal system dispensable for Drosophila head development

In Drosophila, the gradient of the Bicoid (Bcd) morphogen organizes the anteroposterior axis while the ends of the embryo are patterned by the maternal terminal system. At the posterior pole, expression of terminal gap genes is mediated by the local activation of the Torso receptor tyrosine kinase (Tor). At the anterior, terminal gap genes are also activated by the Tor pathway but Bcd contributes to their activation. Evidence is presented that Tor and Bcd act independently on common target genes in an additive manner. Furthermore, the terminal maternal system is shown not to be required for proper head development, since high levels of Bcd activity can functionally rescue the lack of terminal system activity at the anterior pole. This observation is consistent with a recent evolution of an anterior morphogenetic center consisting of Bcd and anterior Tor function (Schaeffer, 2000).

The terminal maternal system directly modifies Bcd by phosphorylation at several MAPK sites in a Ser/Thr (S/T)-rich region located between the homeodomain and the identified transcriptional activation domains. A deletion variant of Bcd that lacks all these activation domains but still contains the S/T-rich region (BcdDeltaQAC) is able to rescue to viability bcd loss-of-function mutants. Hence, it is conceivable that the ability of the tor pathway to create negative charges through phosphorylation of this region of Bcd might result in an acidic-rich transcriptional activation domain that compensates for the loss of all the other activation domains. If this were the case, then the transcriptional activity of the BcdDeltaQAC deletion variant should be highly dependent on tor function. To test this hypothesis, the ability of a BcdDeltaQAC transgene to rescue the bcd phenotype in embryos derived from bcd;tsl double mutant mothers was assayed. BcdDeltaQAC rescues the bcd phenotype of the bcd;tsl double mutant similarly to a wild-type bcd transgene, resulting in a tsl only phenotype. Since BcdDeltaQAC is functionally independent of the tor pathway, it is concluded that the terminal system is not responsible for BcdDeltaQAC's activation potential. This result is also consistent with the notion that, in transient transfection experiments and transgenic studies, Bcd transcriptional activity is not significantly modified by mutations of the putative MAPK consensus sites. Thus, the described direct modification of Bcd by the tor pathway does not appear to be necessary for Bcd's function (Schaeffer, 2000).

tor function is necessary to allow a normal expression pattern of most Bcd target genes: many Bcd target genes such as otd are expressed in a reduced anterior domain in tor mutants. Furthermore, the expression domain of these genes is expanded in tor gain-of-function backgrounds, again suggesting that the tor pathway potentiates Bcd function. This effect could be direct, as Bcd transcriptional activity might be enhanced by direct modification of the protein (for instance by phosphorylation). Alternatively, the effect might be indirect, since most Bcd target promoters might also be responsive to Tor through distinct elements (Schaeffer, 2000).

A direct effect should be detectable with simply organized Bcd target promoters that only contain Bcd-response elements and no Tor-response elements. The proximal hb promoter (P2) resembles such a simple Bcd-response element, which uses activators to set an expression border without the assistance of repressors. The hb P2 promoter is not directly responsive to the terminal pathway; in the absence of Tor activity, the posterior border of hb expression moves only very slightly towards the anterior and, in tor gain-of-function embryos (tor4021), the posterior expression border does not respond significantly to ubiquitously activated Tor (Schaeffer, 2000).

However, the hb P2 promoter is still 300 bp long and might contain elements that are not well defined, and the hb pattern is very dynamic. Therefore, in addition an artificial Bcd responder gene was used whose promoter elements are all known. This promoter contains only Bcd and Hb binding sites (Bcd3Hb3-LacZ), and its expression is reminiscent of the hb P2 promoter, with an anterior cap expression domain from 100% to 65% EL. If Bcd were a direct target of Tor, the posterior border of the reporter gene expression domain should move in response to a tor gain-of-function allele. However, the expression pattern does not change in a tor4021 background. This argues for a Bcd activator function that is not under direct control of the terminal system. Thus, Bcd and Tor seem to be part of two independent pathways, which share common target genes (Schaeffer, 2000).

When a complete series of Bcd deletion variants was assayed for their ability to rescue the bcd loss-of-function phenotype in the absence of terminal system activity, one transgenic line was found that not only rescues the bcd phenotype but also the anterior part of the tsl phenotype (labrum and dorsal bridge), resulting in a posterior terminal mutant phenotype only. This particular transgenic line carries a bcd variant that deletes an alanine-rich domain (BcdDeltaA) and has been shown to activate the bcd target gene hb in a widely enlarged expression domain. Using Bcd immunostaining, it has been shown that this transgenic line exhibits levels of Bcd that are approximately 2- to 3-fold higher than wild type. Since other BcdDeltaA lines did not exhibit the same ability to rescue the tsl phenotype, it is concluded that the higher expression level of this particular line rather than the lack of a specific negative protein element (alanine-rich domain) is responsible for overcoming the requirement for the terminal pathway at the anterior (Schaeffer, 2000).

To further address whether high levels of bcd activity are sufficient to rescue the anterior terminal system phenotype or, if only a particular Bcd deletion variant is capable thereof, the ability of increased doses of wild-type bcd transgenes to rescue several terminal mutant backgrounds was tested. Since the previous experiments were performed with the tsl1 allele, which might only represent a strong hypomorphic allele rather than a null, another tsl mutant, tsl4 , was included that is among the strongest in the allelic series, as well as null mutant alleles of the terminal genes trk and tor. To increase the Bcd expression level, flies containing an X chromosome or a third chromosome each carrying two wild-type bcd rescue constructs were used; these flies carry up to six copies of bcd. The phenotypes of all terminal mutants (tsl, trk or tor) are similar: lack of labrum and dorsal bridge in the anterior and deletion of all structures posterior to A7. Four copies of the bcd gene were able to rescue anterior structures including labrum and dorsal bridge in about 40% of all embryos derived from a tsl4 mutant background, while the posterior terminal phenotype is unaffected. Six copies of bcd are necessary to obtain the same anterior rescue in about 15% of all embryos derived from trk mutants and in about 5% of all embryos derived from tor mutants. However, not all embryos with rescued labrum and dorsal bridge had a perfectly aligned head skeleton. This might be due to incomplete rescue, but it could also be due to Bcd-mediated overexpression of hb at the anterior pole, which results in terminal-like phenotypes (Schaeffer, 2000).

Actually 50%, 70% or 85% of the head cuticles of tsl, trk or tor mutants, respectively, could not be analyzed for rescue due to severe anterior defects, which seemed more severe than normal terminal phenotypes. Nonetheless, some of the rescued embryos (less than 2%) were able to hatch and move around, which suggests complete anterior rescue. These probably represent embryos where just enough Bcd was present to overcome the lack of the terminal system but not too much to induce the phenotype due to high ectopic expression of hb. All larvae died within 2 hours, likely due to the posterior terminal defects. It should be noted that very few embryos exhibited the type of abdominal segment fusions that have been described for embryos derived from mothers carrying excess copies of the bcd gene. This might be due to the lack of terminal system function at the posterior pole in these experiments. Since no tail is made, there is probably more space for fate-map shifts towards the posterior, resulting in the correct establishment of abdominal segments A1 to A6. The rescue of the anterior terminal phenotype by high levels of bcd further indicates that the major role of the anterior terminal system is the potentiation of Bcd activity (Schaeffer, 2000).

In the posterior region of the embryo, the tor pathway activates the zygotic effectors tll and hkb, which are sufficient to specify the most posterior anlagen and the gut of the larva. At the anterior, the function of the terminal system is more difficult to interpret and, in tor mutants, hkb expression is only reduced. It actually requires bcd;tsl double mutants to lose all anterior hkb expression, which indicates additive functions of the anterior and terminal systems on this common target gene. hkb seems particularly interesting in this context, as its function is required for the formation of the labrum: reduction of hkb expression, as observed in terminal mutant background leads to the deletion of this particular structure (Schaeffer, 2000).

Therefore, it was asked whether the rescue of anterior structures (e.g. the labrum) mediated by high levels of Bcd in terminal system mutants is correlated with the restoration of the hkb expression pattern. Expression of hkb is first detected in the terminal regions (anterior and posterior) of the syncytial blastoderm. In terminal mutant embryos, the posterior domain is absent, whereas the anterior domain is reduced. In a tsl background with four or six copies of bcd, however, hkb expression extends further towards the posterior. Hence, the level of hkb expression can be regained by increasing the levels of Bcd in a terminal system mutant, even though its exact expression domain cannot be restored. It is likely that fate-map shifts are able to absorb the slightly changed expression domain of hkb. This suggests that the lack of terminal system activity at the anterior can simply be overcome by another system through enhancement of transcriptional activation of common target genes (Schaeffer, 2000).

Tor has been shown to antagonize Groucho-mediated repression of genes such as hkb and tll, probably by acting on the HMG-box transcription factor Capicua. Therefore, it is likely that Tor enhances Bcd activity by derepression, i.e. the inactivation of potential repressors of Bcd target genes, and thereby rendering any transcriptional activator more potent. As the cis-regulatory control regions of most developmental genes comprise both repressor and activator sites, the inactivation of potential repressors should lead to enhanced expression, or enlarged expression domains, as observed for several bcd target genes in a tor gain-of-function background (Schaeffer, 2000).

Since bcd and tor appear to function independently of each other, it is conceivable that anterior tor activity can also enhance the function of other transcriptional activators through derepression. Therefore, in long-germband insects that might lack a true bcd homolog, the anterior terminal system could also assist other activators, like homologs of Otd or Hb. Moreover, the fact that, in certain situations in the Drosophila embryo, anterior Tor activity can be dispensable for proper head development, is consistent with the observation that a posterior morphogenetic center is more frequently found in insects than an anterior center. Although flies accumulate BCD mRNA and tor activity at the anterior pole of the egg, this might not be useful for most short-germband insects as their embryos develop in the posterior part of the egg. In this case, the anterior of the embryo is far away from the anterior of the egg and the morphogenetic role of bcd and tor would not be effective in patterning the head. In Tribolium castaneum, an intermediate-germband beetle, the activity of the terminal system is conserved at the anterior of the embryo, but it does not appear to have a specific function for pattern formation. Correspondingly, the tll homolog of Tribolium is only expressed at the posterior pole of the embryo. This is in contrast to Drosophila, where tll is expressed at both poles of the early embryo. Moreover, in spite of arguments supporting the presence of a bcd-like function in Tribolium, no bcd homologous gene has been identified outside higher diptera notwithstanding Bcd's homeodomain and bcd's location in the Hox cluster. It is therefore reasonable to assume that an anterior morphogenetic center consisting of Bcd and anterior Tor activity is not a general feature of insects (Schaeffer, 2000).

Homeodomain position 54 specifies transcriptional versus translational control by Bicoid

Bicoid (Bcd) controls embryonic gene expression by transcriptional activation and translational repression. Both functions require the homeodomain (HD), which recognizes DNA motifs at target gene enhancers and a specific sequence interval in the 3' untranslated region of Caudal (CAD) mRNA. The Bcd HD has been shown to be a nucleic acid-binding unit. Its helix III contains an arginine-rich motif (ARM), similar to the RNA-binding domain of the HIV-1 protein REV, needed for both RNA and DNA recognition. Replacement of arginine 54, within this motif, alters the RNA but not the DNA binding properties of the HD. Corresponding BCD mutants fail to repress CAD mRNA translation, whereas the transcriptional target genes are still activated (Niessing, 2000).

In order to characterize portions and individual amino acid residues of the Bcd HD that are specifically required for one or both Bcd regulatory functions, transgenes expressing wild-type or mutant bcd cDNAs were placed into the genome of homozygous bcd mutant females and their ability to rescue wild-type zygotic hb activation and cad mRNA translation in their embryos was assayed. Such embryos, referred to as 'bcd embryos,' fail to exert Bcd-dependent transcriptional activation of the zygotic target gene hb in their anterior half. Instead, the embryos show a duplication of the posterior Bcd-independent stripe of hb expression in the anterior region (Niessing, 2000).

Expressed Bcd mutant proteins that lack the helices I and II of the HD (BcdDeltaH1-2) or the amino acid interval between positions 42 and 51 in helix III (BcdT42-N51) fail to restore Bcd-dependent hb transcriptional activation and translational repression of CAD mRNA in the anterior region of bcd embryos. This indicates that the integrity of the Bcd HD is necessary for the control of transcription and translation. Transgene-dependent expression of BcdhIIIAntp, in which the C-terminal half of the Bcd HD is exchanged for the corresponding sequence of the Antennapedia (Antp) HD, rescues Bcd-dependent hb expression in the anterior region of bcd embryos, but no Cad gradient is formed. Bcd mutations in which two adjacent arginines at positions 53-54 and 54-55 of the HD, respectively, were replaced, fail to control Bcd-dependent transcription and translation. Thus, helix III of the Bcd HD is necessary for both transcriptional activation and translational repression, and amino acids within helix III are essential for specifying not only DNA binding but also RNA recognition by the HD. This proposal is consistent with the observation that part of the helix III of the Bcd HD has characteristics of an arginine-rich motif (ARM) (Niessing, 2000).

To test whether the conserved amino acids of Bcd's ARM are indeed required for RNA target recognition and whether single amino acid replacements may allow the DNA and RNA binding properties to separate, alanine replacement mutants of the Bcd HD were generated and their in vitro binding properties assayed. The Bcd HD (HDwt) binds both DNA and RNA, whereas HDK50A, HDN51A, HDR53A, and HDR55A failed to bind to both targets. Bcd HDR54A, which contains alanine in place of arginine in position 54 of the HD, bound DNA properly, but its RNA binding was reduced by more than one order of magnitude. The binding properties of HDK57A were indistinguishable from HDwt. In summary, arginine at position 54 of the HD is critical for specifying RNA versus DNA binding, and its replacement shifts the binding property of the HD to prefer DNA over RNA recognition (Niessing, 2000).

In order to test the in vivo relevance of these binding studies, the corresponding Bcd HD mutants were examined by transgene-dependent expression in bcd embryos. The Bcd mutants were generated in the context of an 8.7 kb genomic DNA fragment spanning the entire bcd locus, which fully rescues bcd embryos after P element-mediated transformation. The transgene-expressed BcdK57A protein, which contains an HD with normal DNA and RNA binding properties, causes Bcd-dependent hb expression and Cad gradient formation, and the embryos developed into normal-looking larvae and fertile adults. BcdN51A, BcdR53A, and BcdR55A, which contain HD mutations that cause the loss of DNA and RNA binding properties in vitro, fail to activate Bcd-dependent hb transcription and to repress translation of CAD mRNA; such embryos develop a bcd mutant phenotype. The BcdR54A mutant, which contains an HD with DNA, but no RNA, binding properties, was able to activate the transcription of hb but not to repress the translation of CAD mRNA. This observation is consistent with the result obtained using the transgene bearing the BcdR54S mutation, which contains a serine residue in place of arginine at position 54. Thus, both Bcd mutants that contain a replacement of arginine at position 54 of the HD fail to control CAD mRNA translation but do activate transcription of hb (Niessing, 2000).

Mutations of bcd that interfere with the control of CAD mRNA translation but not with the activation of transcription cause temperature-dependent head involution defects. The corresponding larvae develop the normal number and identity of head segments, which, however, fail to be properly assembled. The same phenotype would be expected for the BcdR54A mutant embryos, ensuring that the replacement affects only CAD mRNA translational control. bcd embryos expressing the BcdR54A mutant develop a normal segment pattern at 18°C and give rise to normal-looking and fertile adults. At 29°C, however, the majority of the embryos (more than 90%) die as unhatched larvae, and all of them express a strong head defect. The embryos show a normal expression pattern of the segment polarity gene engrailed (en) at stages 9-11, indicating that segments are generated normally. Furthermore, all discernible head markers can be observed in larval cuticle preparations, but, as observed with mutations affecting the translational repressor region of Bcd, the assembly of the head elements is strongly perturbed. The same temperature-dependent phenotype is observed when cad cDNA lacking the Bcd-responsive BBR in the 3'UTR is expressed in the preblastoderm embryo using the GAL4/UAS system. Taken together, the in vivo transgene studies and the in vitro binding results establish that a single amino acid replacement in the ARM of the Bcd HD specifically interferes with Bcd-dependent RNA binding and translational repression of CAD mRNA, without affecting DNA binding and transcriptional activation. The finding is consistent with the observation that an arginine residue at this position is conserved in ARMs but rare in HDs (Niessing, 2000).

The results provide strong evidence that the Bcd HD functions as a nucleic acid-binding unit that enables Bcd to function in transcriptional and translational control. In addition, the findings establish that the direct interaction of Bcd with the BBR of CAD mRNA shown in vitro is necessary to prevent Cad activity from interfering with head morphogenesis. Helix III of the Bcd HD has been identified as a region in which a single amino acid replacement shifts the in vitro binding property of the HD to prefer DNA over RNA recognition and abolishes CAD mRNA translational repression not affecting transcriptional activation by Bcd in vivo. The alpha-helical structure and sequence comparison between HIV-1 REV and the third helix of the Bcd HD indicate that Bcd formally fits as a member of the ARM family of RNA-binding proteins that show a low degree of amino acid sequence identity. The sequence similarity between the ARMs of HIV-1 REV and the Bcd HD is therefore remarkable. However, there is no corresponding sequence similarity observed between the RNA target sequences to which they bind. Furthermore, REV fails to bind the BBR, and Bcd-HD does not recognize the REV response element. Thus, the high degree of amino acid identity and conservation of the critical arginine residue in the ARMs of the Bcd HD and HIV-1 REV is not correlated with similarity at the level of the targets (Niessing, 2000).

Asparagine is absolutely conserved at position 51 of HDs and is also found in the corresponding position in ARM family members. It has been shown to provide base contacts in DNA/HD complexes and RNA target recognition by ARM proteins, respectively. Consistently, mutation of arginine in position 51 of the Bcd HD abolished DNA binding as well as RNA binding. In contrast, the 52-57 region of HDs interacts with DNA electrostatically, whereas some of the corresponding REV arginine residues are hydrogen bonded to bases. Mutating arginine at position 54, which is rare in other HDs, affects RNA binding without altering the DNA binding. In summary, these and earlier findings with respect to the DNA binding properties of HDs support the proposal that the ARM within the helix III of the Bcd HD is necessary for both RNA and DNA target recognition, and that individual amino acids within this portion of the HD specify RNA versus DNA binding (Niessing, 2000).

Although the Bcd HD is by now the only known HD with RNA binding properties, it has been noted that the ARM-containing RNA-binding domain of EIAV-TAT and the ribosomal protein L11 can fold into HD-like structures with the RNA-binding domain exposed as a helix III equivalent. The recently solved crystal structure of this protein bound to a ribosomal RNA fragment shows binding to the minor groove of RNA that is similar in width to a DNA major groove. The results also indicate that L11 uses the same surface as the HD does in binding DNA. The structural similarities and the fact that helix III regions of HDs are generally rich in basic amino acids suggest that HDs hold a high potential to either exert or to adopt RNA binding properties during evolution. The possibility that other HDs also bind RNAs and thereby provide HD proteins with dual regulatory functions is a challenging proposal (Niessing, 2000 and references therein).


bicoid is located in the Antennapedia complex between Deformed and zerknüllt.
cDNA clone length - 2.6 kb

Bases in 5' UTR - 169

Exons - four

Bases in 3' UTR - 825


Amino Acids - 494

Structural Domains

Bicoid has an N-terminal region, consisting of alternating histidines and prolines, and a central homeodomain. Following the homeodomain there is a region of repetitive glutamines known as an OPA repeat (Berleth, 1988). The homeodomain has no more than 40% homology to any other known homeodomain proteins (Frigerio, 1986)

The maternal gene bicoid (bcd) determines pattern in the anterior half of the Drosophila embryo. It is reported here that the injection of bcd mutant embryos with messenger RNAs that encode proteins consisting of heterologous acidic transcriptional activating sequences fused to the DNA-binding portion of the bcd gene product, can completely restore the anterior pattern of the embryo (Driever, 1989).

Bicoid is a molecular morphogen, controlling embryonic patterning in Drosophila. It is a homeodomain-containing protein that activates specific target genes during early embryogenesis. A domain of Bcd located outside its homeodomain has been identified and referred to as a self-inhibitory domain; this domain can dramatically repress Bicoid's ability to activate transcription. Evidence that the self-inhibitory function is evolutionarily conserved. A systematic analysis of this domain reveals a composite 10-amino acid motif with interdigitating residues that regulate Bcd activity in opposite manners. Mutations within the Bcd motif can exert their respective effects when the self-inhibitory domain is grafted to an entirely heterologous activator, but they do not affect DNA binding in vitro or subcellular localization of Bcd in cells. It is further shown that the self-inhibitory domain of Bcd can interact with Sin3A, a component of the histone deacetylase co-repressor complex. This study suggests that the activity of Bcd is intricately controlled by multiple mechanisms involving the actions of co-repressor proteins (Zhao, 2005).

The solution structure of the homeodomain of the Drosophila morphogenic protein Bicoid (Bcd) complexed with a TAATCC DNA site is described. Bicoid is the only known protein that uses a homeodomain to regulate translation, as well as transcription, by binding to both RNA and DNA during early Drosophila development; in addition, the Bcd homeodomain can recognize an array of different DNA sites. The dual functionality and broad recognition capabilities signify that the Bcd homeodomain may possess unique structural/dynamic properties. Bicoid is the founding member of the K50 class of homeodomain proteins, containing a lysine residue at the critical 50th position (K50) of the homeodomain sequence, a residue required for DNA and RNA recognition; Bcd also has an arginine residue at the 54th position (R54), which is essential for RNA recognition. Bcd is the only known homeodomain with the K50/R54 combination of residues. The Bcd structure indicates that this homeodomain conforms to the conserved topology of the homeodomain motif, but exhibits a significant variation from other homeodomain structures at the end of helix 1. On the consensus TAATCC DNA site, both side-chains make direct and water-mediated contacts to bases in the DNA (ATTAGG for R54, and TAATCC/ATTAGG for K50). A key result is the observation that the side-chains of the DNA-contacting residues K50, N51 and R54 all show strong signs of flexibility in the protein-DNA interface. This finding is supportive of the adaptive-recognition theory of protein-DNA interactions (Baird-Titusa, 2005).


date revised:  23 May 2000 


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