2ims
From Proteopedia
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==Overview== | ==Overview== | ||
| - | BAK/BAX-mediated mitochondrial outer-membrane permeabilization (MOMP) | + | BAK/BAX-mediated mitochondrial outer-membrane permeabilization (MOMP) drives cell death during development and tissue homeostasis from zebrafish to humans. In most cancers, this pathway is inhibited by BCL-2 family antiapoptotic members, which bind and block the action of proapoptotic BCL proteins. We report the 1.5 A crystal structure of calpain-proteolysed BAK, cBAK, to reveal a zinc binding site that regulates its activity via homodimerization. cBAK contains an occluded BH3 peptide binding pocket that binds a BID BH3 peptide only weakly . Nonetheless, cBAK requires activation by truncated BID to induce cytochrome c release in mitochondria isolated from bak/bax double-knockout mouse embryonic fibroblasts. The BAK-mediated MOMP is inhibited by low micromolar zinc levels. This inhibition is alleviated by mutation of the zinc-coordination site in BAK. Our results link directly the antiapoptotic effects of zinc to BAK. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Gehring, K | + | [[Category: Gehring, K B.]] |
[[Category: Liu, Q.]] | [[Category: Liu, Q.]] | ||
[[Category: Moldoveanu, T.]] | [[Category: Moldoveanu, T.]] | ||
| - | [[Category: Shore, G | + | [[Category: Shore, G C.]] |
[[Category: Tocilj, A.]] | [[Category: Tocilj, A.]] | ||
[[Category: Watson, M.]] | [[Category: Watson, M.]] | ||
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[[Category: dimer]] | [[Category: dimer]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:54:07 2008'' |
Revision as of 15:54, 21 February 2008
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The X-ray Structure of a Bak Homodimer Reveals an Inhibitory Zinc Binding Site
Overview
BAK/BAX-mediated mitochondrial outer-membrane permeabilization (MOMP) drives cell death during development and tissue homeostasis from zebrafish to humans. In most cancers, this pathway is inhibited by BCL-2 family antiapoptotic members, which bind and block the action of proapoptotic BCL proteins. We report the 1.5 A crystal structure of calpain-proteolysed BAK, cBAK, to reveal a zinc binding site that regulates its activity via homodimerization. cBAK contains an occluded BH3 peptide binding pocket that binds a BID BH3 peptide only weakly . Nonetheless, cBAK requires activation by truncated BID to induce cytochrome c release in mitochondria isolated from bak/bax double-knockout mouse embryonic fibroblasts. The BAK-mediated MOMP is inhibited by low micromolar zinc levels. This inhibition is alleviated by mutation of the zinc-coordination site in BAK. Our results link directly the antiapoptotic effects of zinc to BAK.
About this Structure
2IMS is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site., Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K, Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251
Page seeded by OCA on Thu Feb 21 17:54:07 2008
Categories: Homo sapiens | Single protein | Gehring, K B. | Liu, Q. | Moldoveanu, T. | Shore, G C. | Tocilj, A. | Watson, M. | ZN | Dimer
