The Structural Biology of Bcl-xL

International Journal of Molecular Sciences

W.Douglas Fairlie¹  ErinnaF. Lee¹ 

[1] Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia;

关键词: apoptosis;    Bcl-2;    Bcl-x_L;    BH3-only;    BH3 domain;    BH3-mimetic;    pro-survival;    structural biology;   

DOI  :  10.3390/ijms20092234

来源: DOAJ

【 摘 要 】

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-x_L. The first high-resolution structure of any Bcl-2 family member was of Bcl-x_L, which revealed the conserved topology amongst all family members. Subsequent structures of Bcl-x_L complexes with pro-apoptotic ligands demonstrated the general features of all pro-survival:pro-apoptotic complexes. Structural studies involving Bcl-x_L 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-x_L and how this has impacted our understanding of the molecular details of the intrinsic apoptotic pathway.

【 授权许可】

Unknown