کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2187456 1096120 2008 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Role of the Conserved Switch II Glutamate in Guanine Nucleotide Exchange Factor-Mediated Nucleotide Exchange of GTP-Binding Proteins
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
The Role of the Conserved Switch II Glutamate in Guanine Nucleotide Exchange Factor-Mediated Nucleotide Exchange of GTP-Binding Proteins
چکیده انگلیسی

Guanine nucleotide exchange factors (GEFs) regulate the activity of small G proteins by catalysing the intrinsically slow exchange of GDP for GTP. The mechanism involves the formation of trimeric G protein-nucleotide–GEF complexes, followed by the release of nucleotide to form stable binary G protein–GEF complexes. A number of structural studies of G protein–GEF complexes have shown large structural changes induced in the nucleotide binding site. Together with a recent structure of a trimeric complex, these studies have suggested not only some common principles but also large differences in detail in the GEF-mediated exchange reaction. Several structures suggested that a glutamic acid residue in switch II, which is part of the DxxGQE motif and highly conserved in Ras-like G proteins, might have a decisive mechanistic role in GEF-mediated nucleotide exchange reactions. Here we show that mutation of the switch II glutamate to Ala severely impairs GEF-catalysed nucleotide exchange in most, but not all, Ras family G proteins, explaining its high sequence conservation. The residue determines the initial approach of GEF to the nucleotide-loaded G protein and does not appreciably affect the formation of a binary nucleotide-free complex. Its major effect thus appears to be the removal of the P-loop lysine from its interaction with the nucleotide.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 379, Issue 1, 23 May 2008, Pages 51–63
نویسندگان
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