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Sci. Signal., 16 September 2008
Vol. 1, Issue 37, p. ra4
[DOI: 10.1126/scisignal.1160755]

RESEARCH ARTICLES

Editor's Summary

Insights into Chemokine-Receptor Interactions
The chemokine stromal cell–derived factor 1 (SDF-1, also known as CXCL12) is the ligand of the chemokine receptor CXCR4, a G protein–coupled receptor (GPCR). This ligand–receptor pair plays important roles in development, leukocyte migration, and metastasis. High-affinity interactions between SDF-1 and CXCR4 depend on the sulfation of three critical tyrosine residues in the extracellular N-terminal region of CXCR4, a posttranslational modification common to other chemokine receptors. Transitions between the monomeric and dimeric forms of SDF-1 have interfered with previous attempts to solve the structure of the SDF-1:CXCR4 complex, which prompted Veldkamp et al. to use a constitutively dimeric form of SDF-1 (SDF12) in their study. In addition to solving the nuclear magnetic resonance structure of the SDF12:CXCR4-N-domain complex and thus determining the structural basis of the recognition of receptor sulfotyrosine residues by the chemokine, the authors also found another use for the dimeric chemokine. Although SDF12 stimulated CXCR4-mediated intracellular Ca2+ mobilization, it was unable to stimulate chemotaxis. Moreover, it inhibited chemotaxis to monomeric SDF-1, which suggests that it may be a useful therapeutic means of targeting CXCR4 activity.

Citation: C. T. Veldkamp, C. Seibert, F. C. Peterson, N. B. De la Cruz, J. C. Haugner, III, H. Basnet, T. P. Sakmar, B. F. Volkman, Structural Basis of CXCR4 Sulfotyrosine Recognition by the Chemokine SDF-1/CXCL12. Sci. Signal. 1, ra4 (2008).

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