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PDBsum entry 5c79
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Signaling protein
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PDB id
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5c79
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References listed in PDB file
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Key reference
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Title
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Molecular basis for cooperative binding of anionic phospholipids to the ph domain of the arf gap asap1.
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Authors
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X.Jian,
W.K.Tang,
P.Zhai,
N.S.Roy,
R.Luo,
J.M.Gruschus,
M.E.Yohe,
P.W.Chen,
Y.Li,
R.A.Byrd,
D.Xia,
P.A.Randazzo.
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Ref.
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Structure, 2015,
23,
1977-1988.
[DOI no: ]
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PubMed id
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Abstract
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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.
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