کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2828464 1162709 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Different conformational dynamics of various active states of β-arrestin1 analyzed by hydrogen/deuterium exchange mass spectrometry
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Different conformational dynamics of various active states of β-arrestin1 analyzed by hydrogen/deuterium exchange mass spectrometry
چکیده انگلیسی

Arrestins have important roles in G protein-coupled receptor (GPCR) signaling including desensitization of GPCRs and G protein-independent signaling. Two major intra-molecular interactions, the polar core and the three-element region, maintain arrestins in the basal conformation by connecting the N- and C-domains. Mutations in these regions that disrupt the polar core (R169E or p44) or the three-element (3A) have been reported to interact with GPCRs in a phosphorylation-independent manner, and thus these mutants are referred to as pre-activated arrestins. On the other hand, deletion of 7 residues in the linker region between N- and C-domains (Δ7) freezes arrestins in the inactive state, which has a much lower binding affinity to GPCRs compared to the wild type form. Although these mutants are widely used for functional studies of arrestins, the conformations of these mutants have not yet been fully elucidated. Here, we analyzed the conformational dynamics of β-arrestin1 with various mutants (R169E, p44, 3A, and Δ7) by hydrogen/deuterium exchange mass spectrometry (HDX-MS). HDX-MS data revealed that pre-activated mutants have more deuterium uptake than the basal state, and also that the regions and degree of increased deuterium uptake differ between pre-activated mutants. Unexpectedly, the inactive mutant also showed increased deuterium uptake in a few regions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 190, Issue 2, May 2015, Pages 250–259
نویسندگان
, , , , ,