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PDBsum entry 3osm
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Lipid binding protein
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PDB id
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3osm
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References listed in PDB file
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Key reference
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Title
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Kinase associated-1 domains drive mark/par1 kinases to membrane targets by binding acidic phospholipids.
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Authors
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K.Moravcevic,
J.M.Mendrola,
K.R.Schmitz,
Y.H.Wang,
D.Slochower,
P.A.Janmey,
M.A.Lemmon.
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Ref.
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Cell, 2010,
143,
966-977.
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PubMed id
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Abstract
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Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles
in location-dependent regulation of many protein kinases. Here, we identify the
KA1 domain (kinase associated-1 domain), found at the C terminus of yeast
septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases,
as a membrane association domain that binds acidic phospholipids. Membrane
localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray
crystallography, we identified a structurally conserved binding site for anionic
phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs
membrane association of both KA1 domains and intact proteins and reveals the
importance of phosphatidylserine for bud neck localization of yeast Kcc4p. Our
data suggest that KA1 domains contribute to "coincidence detection,"
allowing kinases to bind other regulators (such as septins) only at the membrane
surface. These findings have important implications for understanding MARK/PAR1
kinases, which are implicated in Alzheimer's disease, cancer, and autism.
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