Prediction of a Putative Functional Region in the Human Bax Protein by Computational Analysis
- 1 Institutional Program of Molecular Biomedicine, Mexico
Abstract
Structural domains are relevant elements for interactions between Bcl-2 family members to regulate apoptosis and cell survival. Although BH1-BH4 domains can be identified by their sequence and selective occurrence in Bcl-2-family members, structural regions have not been entirely determined yet. The functional residues of Bax, the most representative pro-apoptotic protein of the human Bcl-2 family, remain almost unknown. Here, we identified the human Bax homologues through PSI-Blast analysis. By phylogenetic study, protein sequence multialignment and three-dimensional mapping, we detected the most conserved amino acids in these proteins. Based on these results, we predicted that the human Bax protein has a putative functional region formed by ten relevant residues in BH1 (G103, N106, G108, R109, V111 and A112) and BH2 domains (W151, G157 and W158), as well as outside of them (V95). Interestingly, the structural analysis of this functional region showed that these residues are closely located inside the protein, forming a putative active site. Moreover, this site seems to be protected by the C-terminal end α9 helix that could act as a regulating gate for the access to this region. In addition, the hydrophobic feature of this helix suggests that it could be involved in the insertion into the mitochondrial membrane that is thought to be important for Bcl-2 family members dimerization and activation.
DOI: https://doi.org/10.3844/ajidsp.2007.68.75
Copyright: © 2007 María Sánchez-Aguilar, Laurence A. Marchat and Absalom Zamorano. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- 3,536 Views
- 2,271 Downloads
- 5 Citations
Download
Keywords
- Bcl-2 family
- bioinformatics
- structure
- apoptosis