2YV6

Crystal structure of human Bcl-2 family protein Bak

Summary for 2YV6

• Entry DOI: 10.2210/pdb2yv6/pdb
• Descriptor: Bcl-2 homologous antagonist/killer, SULFATE ION (3 entities in total)
• Functional Keywords: structure genomics, bcl domain, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi, apoptosis
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion membrane; Single-pass membrane protein (Potential): Q16611
• Total number of polymer chains: 1
• Total formula weight: 18737.33

Authors

Wang, H.,Kishishita, S.,Murayama, K.,Takemoto, C.,Terada, T.,Shirouzu, M.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2007-04-09, release date: 2008-04-15, Last modification date: 2024-10-30)

Primary citation

Wang, H.,Takemoto, C.,Akasaka, R.,Uchikubo-Kamo, T.,Kishishita, S.,Murayama, K.,Terada, T.,Chen, L.,Liu, Z.J.,Wang, B.C.,Sugano, S.,Tanaka, A.,Inoue, M.,Kigawa, T.,Shirouzu, M.,Yokoyama, S.
Novel dimerization mode of the human Bcl-2 family protein Bak, a mitochondrial apoptosis regulator.
J.Struct.Biol., 166:32-37, 2009

PubMed 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 2.5A, 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.

PubMed: 19135534
DOI: 10.1016/j.jsb.2008.12.003

Experimental method

X-RAY DIFFRACTION (2.5 Å)