Structural basis of Bcl-xL recognition by a BH3-mimetic α/β-peptide generated by sequence-based design.

ABSTRACT: The crystal structure of a complex between the prosurvival protein Bcl-x(L) and an α/β-peptide 21-mer is described. The α/β-peptide contains six β-amino acid residues distributed periodically throughout the sequence and adopts an α-helix-like conformation that mimics the bioactive shape of the Puma BH3 domain. The α/β-peptide forms all of the noncovalent contacts that have previously been identified as necessary for recognition of the prosurvival protein by an authentic BH3 domain. Comparison of our α/β-peptide:Bcl-x(L) structure with structures of complexes between native BH3 domains and Bcl-2 family proteins reveals how subtle adjustments, including variations in helix radius and helix bowing, allow the α/β-peptide to engage Bcl-x(L) with high affinity. Geometric comparisons of the BH

SUBMITTER: Lee EF 

PROVIDER: S-EPMC3263372 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature