Threading analysis of prospero-type homeodomains.
The homeodomain is a common structural motif found in many transcription factors involved in cell fate determination during development. We have used threading analysis techniques to predict whether the atypical homeodomain of prospero (pros) family members could form the three-helical homeodomain structural motif, even though these proteins are not statistically similar to canonical homeodomains as assessed by BLAST searches. Amino acid sequences of these divergent homeodomain proteins were threaded through the X-ray coordinates of the Drosophila engrailed homeodomain protein [23]. The analysis confirms that the prospero class of homeodomain proteins is indeed capable of forming the homeodomain structure despite its low degree of sequence identity to the canonical homeodomain. Energy calculations indicate that the homeodomain structure is stabilized primarily by hydrophobic interactions between residues at the helical interfaces. Although the atypical prospero-type homeodomain shows very little sequence similarity when compared to other homeodomain proteins, the critical amino acids responsible for maintaining the three-dimensional structure are highly conserved. A number of other homeodomain proteins, such as PHO2p from Saccharomyces and Pax6 from human, were also included in the threading analysis and were shown to be able to form the engrailed structure, indicating that there are no rigid overall sequence requirements for the formation of the homeodomain structural motif. Based on the threading experiments and the subsequent structural alignment, a new amino acid signature that unambiguously identifies the prospero-type proteins was deduced.
Banerjee-Basu
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Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Landsman
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Baxevanis
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D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D029721:Drosophila Proteins; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D013816:Thermodynamics; D014157:Transcription Factors
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C073099:pros protein, Drosophila