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PDBsum entry 2k04
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References listed in PDB file
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Key reference
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Title
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Structural basis of cxcr4 sulfotyrosine recognition by the chemokine sdf-1/cxcl12.
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Authors
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C.T.Veldkamp,
C.Seibert,
F.C.Peterson,
N.B.De la cruz,
J.C.Haugner,
H.Basnet,
T.P.Sakmar,
B.F.Volkman.
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Ref.
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Sci Signal, 2008,
1,
ra4.
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PubMed id
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Abstract
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Stem cell homing and breast cancer metastasis are orchestrated by the chemokine
stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4. Here, we report
the nuclear magnetic resonance structure of a constitutively dimeric SDF-1 in
complex with a CXCR4 fragment that contains three sulfotyrosine residues
important for a high-affinity ligand-receptor interaction. CXCR4 bridged the
SDF-1 dimer interface so that sulfotyrosines sTyr7 and sTyr12 of CXCR4 occupied
positively charged clefts on opposing chemokine subunits. Dimeric SDF-1 induced
intracellular Ca2+ mobilization but had no chemotactic activity; instead, it
prevented native SDF-1-induced chemotaxis, suggesting that it acted as a potent
partial agonist. Our work elucidates the structural basis for sulfotyrosine
recognition in the chemokine-receptor interaction and suggests a strategy for
CXCR4-targeted drug development.
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