5C6R

Crystal structure of PH domain of ASAP1

Summary for 5C6R

• Entry DOI: 10.2210/pdb5c6r/pdb
• Descriptor: Arf-GAP, PHOSPHATE ION, TRIETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: ph domain, aspa1, signaling protein
• Biological source: Mus musculus (Mouse)
• Cellular location: Cytoplasm: Q9QWY8
• Total number of polymer chains: 2
• Total formula weight: 35146.92

Authors

Xia, D.,Tang, W.K. (deposition date: 2015-06-23, release date: 2015-10-07, Last modification date: 2023-09-27)

Primary citation

Jian, X.,Tang, W.K.,Zhai, P.,Roy, N.S.,Luo, R.,Gruschus, J.M.,Yohe, M.E.,Chen, P.W.,Li, Y.,Byrd, R.A.,Xia, D.,Randazzo, P.A.
Molecular Basis for Cooperative Binding of Anionic Phospholipids to the PH Domain of the Arf GAP ASAP1.
Structure, 23:1977-1988, 2015

PubMed 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.

PubMed: 26365802
DOI: 10.1016/j.str.2015.08.008

Experimental method

X-RAY DIFFRACTION (1.8 Å)