Novel dimerization mode of the human Bcl-2 family protein Bak, a mitochondrial apoptosis regulator
| Autor: | Shigeyuki Yokoyama, Takaho Terada, Takanori Kigawa, S. Kishishita, Tomomi Uchikubo-Kamo, Ryogo Akasaka, Makoto Inoue, Zhi-Jie Liu, Mikako Shirouzu, Chie Takemoto, Akiko Tanaka, Sumio Sugano, Kazutaka Murayama, Lirong Chen, Hongfei Wang, Bi-Cheng Wang |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Light Dimer Molecular Sequence Data Crystallography X-Ray chemistry.chemical_compound Protein structure Structural Biology Scattering Radiation Amino Acid Sequence Cysteine Protein Structure Quaternary Peptide sequence chemistry.chemical_classification Sequence Homology Amino Acid Apoptosis Regulator Bcl-2 family Recombinant Proteins Protein Structure Tertiary Cell biology Amino acid Molecular Weight bcl-2 Homologous Antagonist-Killer Protein Proto-Oncogene Proteins c-bcl-2 chemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Cystine Protein Multimerization biological phenomena cell phenomena and immunity Crystallization Hydrophobic and Hydrophilic Interactions Oxidation-Reduction Bcl-2 Homologous Antagonist-Killer Protein |
| Zdroj: | Journal of Structural Biology. 166:32-37 |
| ISSN: | 1047-8477 |
| DOI: | 10.1016/j.jsb.2008.12.003 |
| Popis: | 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 2.5A, 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. |
| Databáze: | OpenAIRE |
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