期刊
JOURNAL OF STRUCTURAL BIOLOGY
卷 166, 期 1, 页码 32-37出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jsb.2008.12.003
关键词
Bcl-2 family protein; Bak; Apoptosis regulator; Crystal structure; Disulfide bridge; Homodimer
资金
- RIKEN Structural Genomics/Proteomics Initiative (RSGI)
- National Project on Protein Structural and Functional Analysis
- Ministry of Education, Culture, Sports, Science and Technology of Japan
Interactions of Bcl-2 family proteins play a regulatory role in mitochondrial apoptosis. The pro-apoptotic protein Bak resides in the outer mitochondrial membrane, and the formation of Bak homo- or heterodimers is involved in the regulation of apoptosis. The previously reported structure of the human Bak protein (residues Glu16-Gly186) revealed that a zinc ion was coordinated with two pairs of Asp160 and His164 residues from the symmetry-related molecules. This zinc-dependent homodimer was regarded as an anti-apoptotic dimer. In the present study, we determined the crystal structure of the human Bak residues Ser23-Asn185 at 2.5 angstrom, and found a distinct type of homodimerization through Cys166 disulfide bridging between the symmetry-related molecules. In the two modes of homodimerization, the molecular interfaces are completely different. In the membrane-targeted model of the S-S bridged dimer, the BH3 motifs are too close to the membrane to interact directly with the anti-apoptotic relatives, such as Bcl-x(L). Therefore, the Bak dimer structure reported here may represent a pro-apoptotic mode under oxidized conditions. (C) 2008 Elsevier Inc. All rights reserved.
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