کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2030277 1071061 2008 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Crystal Structure of the CaV2 IQ Domain in Complex with Ca2+/Calmodulin: High-Resolution Mechanistic Implications for Channel Regulation by Ca2+
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Crystal Structure of the CaV2 IQ Domain in Complex with Ca2+/Calmodulin: High-Resolution Mechanistic Implications for Channel Regulation by Ca2+
چکیده انگلیسی

SummaryCalmodulin (CaM) regulation of Ca2+ channels is central to Ca2+ signaling. CaV1 versus CaV2 classes of these channels exhibit divergent forms of regulation, potentially relating to customized CaM/IQ interactions among different channels. Here we report the crystal structures for the Ca2+/CaM IQ domains of both CaV2.1 and CaV2.3 channels. These highly similar structures emphasize that major CaM contacts with the IQ domain extend well upstream of traditional consensus residues. Surprisingly, upstream mutations strongly diminished CaV2.1 regulation, whereas downstream perturbations had limited effects. Furthermore, our CaV2 structures closely resemble published Ca2+/CaM-CaV1.2 IQ structures, arguing against CaV1/2 regulatory differences based solely on contrasting CaM/IQ conformations. Instead, alanine scanning of the CaV2.1 IQ domain, combined with structure-based molecular simulation of corresponding CaM/IQ binding energy perturbations, suggests that the C lobe of CaM partially dislodges from the IQ element during channel regulation, allowing exposed IQ residues to trigger regulation via isoform-specific interactions with alternative channel regions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 16, Issue 4, 8 April 2008, Pages 607–620
نویسندگان
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