Abstract
Homeodomains are 60 amino acid DNA binding domains found in numerous eukaryotic transcription factors. The homeodomain family is a useful system for studying sequence-structure relationships because several hundred sequences are known and the structures of several homeodomains have been determined. Covariation of amino acid residues in the homeodomain family has been investigated to see whether strongly covariant residue pairs can be understood in terms of the structure and function of these domains. Among 16 strongly covariant pairs examined, 2 are explained by the ability to form salt bridges, and 9 appear related to the DNA binding function of the proteins. For the remaining 5 pairs, the rationale for covariance remains unclear and the likelihood of artifactual correlations is discussed in the context of experimental and evolutionary biases in the selection of sequences. No significant correlation was found between covariance and structural proximity in the hydrophobic core.
Full Text
The Full Text of this article is available as a PDF (2.5 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Billeter M., Qian Y. Q., Otting G., Müller M., Gehring W., Wüthrich K. Determination of the nuclear magnetic resonance solution structure of an Antennapedia homeodomain-DNA complex. J Mol Biol. 1993 Dec 20;234(4):1084–1093. doi: 10.1006/jmbi.1993.1661. [DOI] [PubMed] [Google Scholar]
- Clarke N. D., Kissinger C. R., Desjarlais J., Gilliland G. L., Pabo C. O. Structural studies of the engrailed homeodomain. Protein Sci. 1994 Oct;3(10):1779–1787. doi: 10.1002/pro.5560031018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Göbel U., Sander C., Schneider R., Valencia A. Correlated mutations and residue contacts in proteins. Proteins. 1994 Apr;18(4):309–317. doi: 10.1002/prot.340180402. [DOI] [PubMed] [Google Scholar]
- Kappen C., Schughart K., Ruddle F. H. Early evolutionary origin of major homeodomain sequence classes. Genomics. 1993 Oct;18(1):54–70. doi: 10.1006/geno.1993.1426. [DOI] [PubMed] [Google Scholar]
- Kissinger C. R., Liu B. S., Martin-Blanco E., Kornberg T. B., Pabo C. O. Crystal structure of an engrailed homeodomain-DNA complex at 2.8 A resolution: a framework for understanding homeodomain-DNA interactions. Cell. 1990 Nov 2;63(3):579–590. doi: 10.1016/0092-8674(90)90453-l. [DOI] [PubMed] [Google Scholar]
- Klemm J. D., Rould M. A., Aurora R., Herr W., Pabo C. O. Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules. Cell. 1994 Apr 8;77(1):21–32. doi: 10.1016/0092-8674(94)90231-3. [DOI] [PubMed] [Google Scholar]
- Korber B. T., Farber R. M., Wolpert D. H., Lapedes A. S. Covariation of mutations in the V3 loop of human immunodeficiency virus type 1 envelope protein: an information theoretic analysis. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7176–7180. doi: 10.1073/pnas.90.15.7176. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laughon A. DNA binding specificity of homeodomains. Biochemistry. 1991 Dec 3;30(48):11357–11367. doi: 10.1021/bi00112a001. [DOI] [PubMed] [Google Scholar]
- Neher E. How frequent are correlated changes in families of protein sequences? Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):98–102. doi: 10.1073/pnas.91.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Qian Y. Q., Billeter M., Otting G., Müller M., Gehring W. J., Wüthrich K. The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: comparison with prokaryotic repressors. Cell. 1989 Nov 3;59(3):573–580. doi: 10.1016/0092-8674(89)90040-8. [DOI] [PubMed] [Google Scholar]
- Qian Y. Q., Furukubo-Tokunaga K., Resendez-Perez D., Müller M., Gehring W. J., Wüthrich K. Nuclear magnetic resonance solution structure of the fushi tarazu homeodomain from Drosophila and comparison with the Antennapedia homeodomain. J Mol Biol. 1994 May 6;238(3):333–345. doi: 10.1006/jmbi.1994.1296. [DOI] [PubMed] [Google Scholar]