1o0l

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(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==
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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.
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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==
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1O0L OCA].
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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]]
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[[Category: Day, C.L.]]
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[[Category: Day, C L.]]
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[[Category: Harrison, P.J.]]
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[[Category: Harrison, P J.]]
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[[Category: Hinds, M.G.]]
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[[Category: Hinds, M G.]]
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[[Category: Huang, D.C.S.]]
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[[Category: Huang, D C.S.]]
[[Category: Lackmann, M.]]
[[Category: Lackmann, M.]]
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[[Category: Skea, G.L.]]
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[[Category: Skea, G L.]]
[[Category: apoptosis]]
[[Category: apoptosis]]
[[Category: bcl-2]]
[[Category: bcl-2]]
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[[Category: helical bundle]]
[[Category: helical bundle]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:27:56 2007''
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''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


1o0l

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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

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