Structure-based redesign of the binding specificity of anti-apoptotic Bcl-x(L).

ABSTRACT: Many native proteins are multi-specific and interact with numerous partners, which can confound analysis of their functions. Protein design provides a potential route to generating synthetic variants of native proteins with more selective binding profiles. Redesigned proteins could be used as research tools, diagnostics or therapeutics. In this work, we used a library screening approach to reengineer the multi-specific anti-apoptotic protein Bcl-x(L) to remove its interactions with many of its binding partners, making it a high-affinity and selective binder of the BH3 region of pro-apoptotic protein Bad. To overcome the enormity of the potential Bcl-x(L) sequence space, we developed and applied a computational/experimental framework that used protein structure information to generate focus

SUBMITTER: Chen TS 

PROVIDER: S-EPMC3557458 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature