1o0l
From Proteopedia
(New page: 200px<br /> <applet load="1o0l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1o0l" /> '''THE STRUCTURE OF BCL-W REVEALS A ROLE FOR T...) |
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'''THE STRUCTURE OF BCL-W REVEALS A ROLE FOR THE C-TERMINAL RESIDUES IN MODULATING BIOLOGICAL ACTIVITY'''<br /> | '''THE STRUCTURE OF BCL-W REVEALS A ROLE FOR THE C-TERMINAL RESIDUES IN MODULATING BIOLOGICAL ACTIVITY'''<br /> | ||
==Overview== | ==Overview== | ||
- | Pro-survival Bcl-2-related proteins, critical regulators of apoptosis, contain a hydrophobic groove targeted for binding by the BH3 domain of the | + | 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. |
==About this Structure== | ==About this Structure== | ||
- | 1O0L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1O0L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O0L OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
- | [[Category: Day, C | + | [[Category: Day, C L.]] |
- | [[Category: Harrison, P | + | [[Category: Harrison, P J.]] |
- | [[Category: Hinds, M | + | [[Category: Hinds, M G.]] |
- | [[Category: Huang, D | + | [[Category: Huang, D C.S.]] |
[[Category: Lackmann, M.]] | [[Category: Lackmann, M.]] | ||
- | [[Category: Skea, G | + | [[Category: Skea, G L.]] |
[[Category: apoptosis]] | [[Category: apoptosis]] | ||
[[Category: bcl-2]] | [[Category: bcl-2]] | ||
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[[Category: helical bundle]] | [[Category: helical bundle]] | ||
- | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:12:03 2008'' |
Revision as of 12:12, 21 February 2008
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THE STRUCTURE OF BCL-W REVEALS A ROLE FOR THE C-TERMINAL RESIDUES IN MODULATING BIOLOGICAL ACTIVITY
Overview
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.
About this Structure
1O0L is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 14:12:03 2008
Categories: Homo sapiens | Single protein | Day, C L. | Harrison, P J. | Hinds, M G. | Huang, D C.S. | Lackmann, M. | Skea, G L. | Apoptosis | Bcl-2 | Bh3 | Binding groove | Helical bundle