Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5915164 | Journal of Structural Biology | 2009 | 6 Pages |
Abstract
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 2.5Â Ã
, 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-xL. Therefore, the Bak dimer structure reported here may represent a pro-apoptotic mode under oxidized conditions.
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Authors
Hongfei Wang, Chie Takemoto, Ryogo Akasaka, Tomomi Uchikubo-Kamo, Seiichiro Kishishita, Kazutaka Murayama, Takaho Terada, Lirong Chen, Zhi-Jie Liu, Bi-Cheng Wang, Sumio Sugano, Akiko Tanaka, Makoto Inoue, Takanori Kigawa, Mikako Shirouzu,