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PDBsum entry 4jl7
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Signaling protein
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PDB id
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4jl7
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PDB id:
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| Name: |
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Signaling protein
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Title:
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Crystal structure of the chemokine receptor cxcr2 in complex with the first pdz domain of nherf1
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Structure:
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Na(+)/h(+) exchange regulatory cofactor nhe-rf1. Chain: a. Fragment: unp residues 11-95. Synonym: nherf-1, ezrin-radixin-moesin-binding phosphoprotein 50, ebp50, regulatory cofactor of na(+)/h(+) exchanger, sodium-hydrogen exchanger regulatory factor 1, solute carrier family 9 isoform a3 regulatory factor 1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: nherf, nherf1, slc9a3r1. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.16Å
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R-factor:
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0.187
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R-free:
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0.208
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Authors:
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G.Lu,Y.Wu,Y.Jiang,J.Brunzelle,N.Sirinupong,C.Li,Z.Yang
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Key ref:
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G.Lu
et al.
(2013).
Structural insights into neutrophilic migration revealed by the crystal structure of the chemokine receptor CXCR2 in complex with the first PDZ domain of NHERF1.
Plos One,
8,
e76219.
PubMed id:
DOI:
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Date:
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12-Mar-13
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Release date:
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23-Oct-13
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PROCHECK
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Headers
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References
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O14745
(NHRF1_HUMAN) -
Na(+)/H(+) exchange regulatory cofactor NHE-RF1 from Homo sapiens
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Seq:
Struc:
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358 a.a.
91 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 5 residue positions (black
crosses)
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DOI no:
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Plos One
8:e76219
(2013)
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PubMed id:
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Structural insights into neutrophilic migration revealed by the crystal structure of the chemokine receptor CXCR2 in complex with the first PDZ domain of NHERF1.
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G.Lu,
Y.Wu,
Y.Jiang,
S.Wang,
Y.Hou,
X.Guan,
J.Brunzelle,
N.Sirinupong,
S.Sheng,
C.Li,
Z.Yang.
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ABSTRACT
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Neutrophil plays an essential role in host defense against infection, but
uncontrolled neutrophilic infiltration can cause inflammation and severe
epithelial damage. We recently showed that CXCR2 formed a signaling complex with
NHERF1 and PLC-2, and that the formation of this complex was required for
intracellular calcium mobilization and neutrophilic transepithelial migration.
To uncover the structural basis of the complex formation, we report here the
crystal structure of the NHERF1 PDZ1 domain in complex with the C-terminal
sequence of CXCR2 at 1.16 Å resolution. The structure reveals that the CXCR2
peptide binds to PDZ1 in an extended conformation with the last four residues
making specific side chain interactions. Remarkably, comparison of the structure
to previously studied PDZ1 domains has allowed the identification of PDZ1
ligand-specific interactions and the mechanisms that govern PDZ1 target
selection diversities. In addition, we show that CXCR2 can bind both NHERF1 PDZ1
and PDZ2 in pulldown experiments, consistent with the observation that the
peptide binding pockets of these two PDZ domains are highly structurally
conserved. The results of this study therefore provide structural basis for the
CXCR2-mediated neutrophilic migration and could have important clinical
applications in the prevention and treatment of numerous neutrophil-dependent
inflammatory disorders.
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Links
