Crystal Structure of a BCL-W Domain-Swapped Dimer: Implications for the Function of BCL-2 Family Proteins
Details
Publication Year 2011-10-12, Volume 19, Issue #10, Page 1467-1476
Journal Title
STRUCTURE
Publication Type
Journal Article
Abstract
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 alpha 3 and alpha 4 hinging away from the core of the protein. Biochemical and functional studies reveal that the alpha 4-alpha 5 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.
Publisher
CELL PRESS
Keywords
SIZE-DISTRIBUTION ANALYSIS; MAXIMUM-LIKELIHOOD; LIPID-MEMBRANES; BAX; APOPTOSIS; BCL-X(L); OLIGOMERIZATION; DIMERIZATION; BINDING; ULTRACENTRIFUGATION
Rights Notice
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Creation Date: 2011-10-12 12:00:00
Last Modified: 0001-01-01 12:00:00
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