کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6139731 1594243 2014 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A computational analysis of the structural determinants of APOBEC3's catalytic activity and vulnerability to HIV-1 Vif
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
A computational analysis of the structural determinants of APOBEC3's catalytic activity and vulnerability to HIV-1 Vif
چکیده انگلیسی
APOBEC3s (A3) are Zn2+ dependent cytidine deaminases with diverse biological functions and implications for cancer and immunity. Four of the seven human A3s restrict HIV by 'hypermutating' the reverse-transcribed viral genomic DNA. HIV Virion Infectivity Factor (Vif) counters this restriction by targeting A3s to proteasomal degradation. However, there is no apparent correlation between catalytic activity, Vif binding, and sequence similarity between A3 domains. Our comparative structural analysis reveals features required for binding Vif and features influencing polynucleotide deaminase activity in A3 proteins. All Vif-binding A3s share a negatively charged surface region that includes residues previously implicated in binding the highly-positively charged Vif. Additionally, catalytically active A3s share a positively charged groove near the Zn2+ coordinating active site, which may accommodate the negatively charged polynucleotide substrate. Our findings suggest surface electrostatics, as well as the spatial extent of substrate accommodating region, are critical determinants of substrate and Vif binding across A3 proteins with implications for anti-retroviral and anti-cancer therapeutic design.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volumes 471–473, December 2014, Pages 105-116
نویسندگان
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