Structural highlights
Function
[B2CL2_HUMAN] Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Pro-survival Bcl-2-related proteins, critical regulators of apoptosis, contain a hydrophobic groove targeted for binding by the BH3 domain of the pro-apoptotic BH3-only proteins. The solution structure of the pro-survival protein Bcl-w, presented here, reveals that the binding groove is not freely accessible as predicted by previous structures of pro-survival Bcl-2-like molecules. Unexpectedly, the groove appears to be occluded by the C-terminal residues. Binding and kinetic data suggest that the C-terminal residues of Bcl-w and Bcl-x(L) modulate pro-survival activity by regulating ligand access to the groove. Binding of the BH3-only proteins, critical for cell death initiation, is likely to displace the hydrophobic C-terminal region of Bcl-w and Bcl-x(L). Moreover, Bcl-w does not act only by sequestering the BH3-only proteins. There fore, pro-survival Bcl-2-like molecules probably control the activation of downstream effectors by a mechanism that remains to be elucidated.
The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity.,Hinds MG, Lackmann M, Skea GL, Harrison PJ, Huang DC, Day CL EMBO J. 2003 Apr 1;22(7):1497-507. PMID:12660157[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S. bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene. 1996 Aug 15;13(4):665-75. PMID:8761287
- ↑ Hinds MG, Lackmann M, Skea GL, Harrison PJ, Huang DC, Day CL. The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity. EMBO J. 2003 Apr 1;22(7):1497-507. PMID:12660157 doi:10.1093/emboj/cdg144