2k04

From Proteopedia

Structure of SDF1 in complex with the CXCR4 N-terminus containing no sulfotyrosines

Structural highlights

2k04 is a 4 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12.,Veldkamp CT, Seibert C, Peterson FC, De la Cruz NB, Haugner JC 3rd, Basnet H, Sakmar TP, Volkman BF Sci Signal. 2008 Sep 16;1(37):ra4. PMID:18799424^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Veldkamp CT, Seibert C, Peterson FC, De la Cruz NB, Haugner JC 3rd, Basnet H, Sakmar TP, Volkman BF. Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12. Sci Signal. 2008 Sep 16;1(37):ra4. PMID:18799424 doi:1/37/ra4