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PDBsum entry 2m0v
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Protein binding/protein binding
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PDB id
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2m0v
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References listed in PDB file
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Key reference
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Title
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Ligand-Induced dynamic changes in extended pdz domains from nherf1.
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Authors
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S.Bhattacharya,
J.H.Ju,
N.Orlova,
J.A.Khajeh,
D.Cowburn,
Z.Bu.
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Ref.
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J Mol Biol, 2013,
425,
2509-2528.
[DOI no: ]
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PubMed id
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Abstract
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The multi-domain scaffolding protein NHERF1 modulates the assembly and
intracellular trafficking of various transmembrane receptors and ion-transport
proteins. The two PDZ (postsynaptic density 95/disk large/zonula occluden 1)
domains of NHERF1 possess very different ligand-binding capabilities: PDZ1
recognizes a variety of membrane proteins with high affinity, while PDZ2 only
binds limited number of target proteins. Here using NMR, we have determined the
structural and dynamic mechanisms that differentiate the binding affinities of
the two PDZ domains, for the type 1 PDZ-binding motif (QDTRL) in the carboxyl
terminus of cystic fibrosis transmembrane regulator. Similar to PDZ2, we have
identified a helix-loop-helix subdomain coupled to the canonical PDZ1 domain.
The extended PDZ1 domain is highly flexible with correlated backbone motions on
fast and slow timescales, while the extended PDZ2 domain is relatively rigid.
The malleability of the extended PDZ1 structure facilitates the transmission of
conformational changes at the ligand-binding site to the remote helix-loop-helix
extension. By contrast, ligand binding has only modest effects on the
conformation and dynamics of the extended PDZ2 domain. The study shows that
ligand-induced structural and dynamic changes coupled with sequence variation at
the putative PDZ binding site dictate ligand selectivity and binding affinity of
the two PDZ domains of NHERF1.
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