کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1929193 1050448 2012 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Crystal structure of Rab6A′(Q72L) mutant reveals unexpected GDP/Mg2+ binding with opened GTP-binding domain
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Crystal structure of Rab6A′(Q72L) mutant reveals unexpected GDP/Mg2+ binding with opened GTP-binding domain
چکیده انگلیسی

The Ras small G protein-superfamily is a family of GTP hydrolases whose activity is regulated by GTP/GDP binding states. Rab6A, a member of the Ras superfamily, is involved in the regulation of vesicle trafficking, which is critical for endocytosis, biosynthesis, secretion, cell differentiation and cell growth. Rab6A exists in two isoforms, termed RabA and Rab6A′. Substitution of Gln72 to Leu72 (Q72L) at Rab6 family blocks GTP hydrolysis activity and this mutation usually causes the Rab6 protein to be constitutively in an active form. Here, we report the crystal structure of the human Rab6A′(Q72L) mutant form at 1.9 Å resolution. Unexpectedly, we found that Rab6A′(Q72L) possesses GDP/Mg2+ in the GTP binding pockets, which is formed by a flexible switch I and switch II. Large conformational changes were also detected in the switch I and switch II regions. Our structure revealed that the non-hydrolysable, constitutively active form of Rab6A′ can accommodate GDP/Mg2+ in the open conformation.


► We solved the structure of Rab6A′(Q72L) mutant.
► We found that the QL mutant possess GDP/Mg2+ unexpectedly.
► We found the large conformational changes in the switch I and switch II regions.
► Our structure show that constitutively active form of Rab6A′ can accommodate GDP/Mg2+ in the open conformation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 424, Issue 2, 27 July 2012, Pages 269–273
نویسندگان
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