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2imt
From Proteopedia
| 2imt, resolution 1.49Å () | |||||||||
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| Ligands: | |||||||||
| Gene: | BAK1, BAK, BCL2L7 (Homo sapiens) | ||||||||
| Domains: | Bcl-2 | ||||||||
| Related: | 1maz, 1f16, 1lxl, 1bxl, 1mk3, 1wsx, 2ims | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
The X-ray Structure of a Bak Homodimer Reveals an Inhibitory Zinc Binding Site
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2IMT is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K. The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site. Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251 doi:10.1016/j.molcel.2006.10.014
Page seeded by OCA on Mon Feb 16 23:41:34 2009
Categories: Homo sapiens | Gehring, K B. | Liu, Q. | Moldoveanu, T. | Shore, G C. | Tocilj, A. | Watson, M. | Dimer

