2y6w

Publication Abstract from PubMed

The prosurvival and proapoptotic proteins of the BCL-2 family share a similar three-dimensional fold despite their opposing functions. However, many biochemical studies highlight the requirement for conformational changes for the functioning of both types of proteins, although structural data to support such changes remain elusive. Here, we describe the X-ray structure of dimeric BCL-W that reveals a major conformational change involving helices alpha3 and alpha4 hinging away from the core of the protein. Biochemical and functional studies reveal that the alpha4-alpha5 hinge region is required for dimerization of BCL-W, and functioning of both pro- and antiapoptotic BCL-2 proteins. Hence, this structure reveals a conformational flexibility not seen in previous BCL-2 protein structures and provides insights into how these regulators of apoptosis can change conformation to exert their function.

Crystal Structure of a BCL-W Domain-Swapped Dimer: Implications for the Function of BCL-2 Family Proteins.,Lee EF, Dewson G, Smith BJ, Evangelista M, Pettikiriarachchi A, Dogovski C, Perugini MA, Colman PM, Fairlie WD Structure. 2011 Oct 12;19(10):1467-76. PMID:22000515^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.