 |
PDBsum entry 3hpm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Protein binding
|
PDB id
|
|
|
|
3hpm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Redox-Regulated lipid membrane binding of the pick1 pdz domain.
|
|
|
Authors
|
|
Y.Shi,
J.Yu,
Y.Jia,
L.Pan,
C.Shen,
J.Xia,
M.Zhang.
|
|
|
Ref.
|
|
Biochemistry, 2010,
49,
4432-4439.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
PICK1 is a PDZ/BAR domain-containing scaffold protein that regulates the
trafficking of many receptors and ion channels, including AMPA receptors. In
addition to binding to a wide spectrum of target proteins to be transported, the
PICK1 PDZ domain, via its conserved CPC motif, has also been shown to bind to
lipid membranes. However, the molecular basis of the CPC motif-mediated lipid
membrane binding of the PICK1 PDZ domain is not known. Here we show that the Cys
residues in the CPC motif of the PICK1 PDZ domain forms reversible,
intermolecular disulfide bonds under mild oxidation conditions. Importantly,
formation of the disulfide-mediated dimer abolishes the lipid membrane binding
capacity of the PICK1 PDZ domain and thereby is expected to alter the cellular
functions of PICK1. The structures of the PDZ dimers provide atomic-scale
pictures of disulfide-mediated PICK1 dimer formation and a molecular explanation
of the oxidation-induced dissociation of PICK1 from membranes. We propose that
the PICK1-mediated trafficking processes might be regulated by cellular redox
fluctuations under both physiological and pathophysiological conditions.
|
|
|
|
|
|
|
