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Biochemistry. 2016 Mar 1;55(8):1214-25. doi: 10.1021/acs.biochem.5b01329. Epub 2016 Feb 17.

Examination of Glycosaminoglycan Binding Sites on the XCL1 Dimer.

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Department of Biochemistry, Medical College of Wisconsin , Milwaukee, Wisconsin 53226, United States.
Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology, University of California at San Diego , La Jolla, California 92093, United States.
Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute , Troy, New York 12180, United States.
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute , Troy, New York 12180, United States.


Known for its distinct metamorphic behavior, XCL1 interconverts between a canonical chemokine folded monomer (XCL1mon) that interacts with the receptor, XCR1, and a unique dimer (XCL1dim) that interacts with glycosaminoglycans and inhibits HIV-1 activity. This study presents the first detailed analysis of the GAG binding properties of XCL1dim. Basic residues within a conformationally selective dimeric variant of XCL1 (W55D) were mutated and analyzed for their effects on heparin binding. Mutation of Arg23 and Arg43 greatly diminished the level of heparin binding in both heparin Sepharose chromatography and surface plasmon resonance assays. To assess the contributions of different GAG structures to XCL1 binding, we developed a solution fluorescence polarization assay and correlated affinity with the length and level of sulfation of heparan sulfate oligosaccharides. It was recently demonstrated that the XCL1 GAG binding form, XCL1dim, is responsible for preventing HIV-1 infection through interactions with gp120. This study defines a GAG binding surface on XCL1dim that includes residues that are important for HIV-1 inhibition.

[Available on 2017-03-01]
[Indexed for MEDLINE]
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