کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5915164 1162789 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel dimerization mode of the human Bcl-2 family protein Bak, a mitochondrial apoptosis regulator
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Novel dimerization mode of the human Bcl-2 family protein Bak, a mitochondrial apoptosis regulator
چکیده انگلیسی
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 Å, 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 166, Issue 1, April 2009, Pages 32-37
نویسندگان
, , , , , , , , , , , , , , ,