title: Crystal structure of a BCL-W domain-swapped dimer: implications for the function of BCL-2 family proteins.
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 α3 and α4 hinging away from the core of the protein. Biochemical and functional studies reveal that the α4-α5 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.
authors: Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors: Erinna F
authors: EF
authors: Lee
authors: Grant
authors: G
authors: Dewson
authors: Brian J
authors: BJ
authors: Smith
authors: Marco
authors: M
authors: Evangelista
authors: Anne
authors: A
authors: Pettikiriarachchi
authors: Con
authors: C
authors: Dogovski
authors: Matthew A
authors: MA
authors: Perugini
authors: Peter M
authors: PM
authors: Colman
authors: W Douglas
authors: WD
authors: Fairlie
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry*; D002151:Calorimetry / Q000379:methods; D002458:Cell Fractionation; D002460:Cell Line; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D007544:Isopropyl Thiogalactoside / Q000737:chemistry; D051379:Mice; D051336:Mitochondrial Membranes / Q000737:chemistry*; D024101:Mitochondrial Proteins / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014461:Ultracentrifugation
chemical_list: D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; C101155:Bcl2l2 protein, mouse; D024101:Mitochondrial Proteins; D011506:Proteins; D007544:Isopropyl Thiogalactoside