| Literature DB >> 26365802 |
Xiaoying Jian1, Wai-Kwan Tang2, Peng Zhai1, Neeladri Sekhar Roy1, Ruibai Luo1, James M Gruschus3, Marielle E Yohe4, Pei-Wen Chen1, Yifei Li5, R Andrew Byrd5, Di Xia6, Paul A Randazzo7.
Abstract
We have defined the molecular basis for association of the PH domain of the Arf GAP ASAP1 with phospholipid bilayers. Structures of the unliganded and dibutyryl PtdIns(4,5)P2-bound PH domain were solved. PtdIns(4,5)P2 made contact with both a canonical site (C site) and an atypical site (A site). We hypothesized cooperative binding of PtdIns(4,5)P2 to the C site and a nonspecific anionic phospholipid to the A site. PtdIns(4,5)P2 dependence of binding to large unilamellar vesicles and GAP activity was sigmoidal, consistent with cooperative sites. In contrast, PtdIns(4,5)P2 binding to the PH domain of PLC δ1 was hyperbolic. Mutation of amino acids in either the C or A site resulted in decreased PtdIns(4,5)P2-dependent binding to vesicles and decreased GAP activity. The results support the idea of cooperative phospholipid binding to the C and A sites of the PH domain of ASAP1. We propose that the mechanism underlies rapid switching between active and inactive ASAP1.Entities:
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Year: 2015 PMID： 26365802 PMCID： PMC4788500 DOI： 10.1016/j.str.2015.08.008
Source DB: PubMed Journal: Structure ISSN： 0969-2126 Impact factor: 5.006