1O0L

THE STRUCTURE OF BCL-W REVEALS A ROLE FOR THE C-TERMINAL RESIDUES IN MODULATING BIOLOGICAL ACTIVITY

Summary for 1O0L

• Entry DOI: 10.2210/pdb1o0l/pdb
• Descriptor: Apoptosis regulator Bcl-W (1 entity in total)
• Functional Keywords: apoptosis, bcl-2, helical bundle, binding groove, bh3
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion membrane; Peripheral membrane protein: Q92843
• Total number of polymer chains: 1
• Total formula weight: 20254.68

Authors

Hinds, M.G.,Lackmann, M.,Skea, G.L.,Harrison, P.J.,Huang, D.C.S.,Day, C.L. (deposition date: 2003-02-22, release date: 2003-04-01, Last modification date: 2024-05-22)

Primary citation

Hinds, M.G.,Lackmann, M.,Skea, G.L.,Harrison, P.J.,Huang, D.C.S.,Day, C.L.
The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity
Embo J., 22:1497-1507, 2003

PubMed Abstract: 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.

PubMed: 12660157
DOI: 10.1093/emboj/cdg144

Experimental method

SOLUTION NMR