The Structural Biology of Bcl-xL

Int J Mol Sci. 2019 May 7;20(9):2234. doi: 10.3390/ijms20092234.

Abstract

Interactions between the pro-survival and pro-apoptotic members of the Bcl-2 family of proteins dictate whether a cell lives or dies. Much of our knowledge of the molecular details of these interactions has come from biochemical and structural studies on the pro-survival protein Bcl-xL. The first high-resolution structure of any Bcl-2 family member was of Bcl-xL, which revealed the conserved topology amongst all family members. Subsequent structures of Bcl-xL complexes with pro-apoptotic ligands demonstrated the general features of all pro-survival:pro-apoptotic complexes. Structural studies involving Bcl-xL were also the basis for the discovery of the first small-molecule pro-survival protein inhibitors, leading ultimately to the development of a new class of drugs now successfully used for cancer treatment in the clinic. This article will review our current knowledge of the structural biology of Bcl-xL and how this has impacted our understanding of the molecular details of the intrinsic apoptotic pathway.

Keywords: BH3 domain; BH3-mimetic; BH3-only; Bcl-2; Bcl-xL; apoptosis; pro-survival; structural biology.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Humans
  • Protein Binding
  • Protein Multimerization
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-X Protein / chemistry*
  • bcl-X Protein / metabolism

Substances

  • Tumor Suppressor Protein p53
  • bcl-X Protein