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Examination of Glycosaminoglycan Binding Sites on the XCL1 Dimer. Biochemistry 2016 Mar 01;55(8):1214-25 PMID: 26836755 PMCID: PMC4775286


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.

Author List

Fox JC, Tyler RC, Peterson FC, Dyer DP, Zhang F, Linhardt RJ, Handel TM, Volkman BF


Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Binding Sites
Chemokines, C
HIV Infections
Heparitin Sulfate
Models, Molecular
Point Mutation
Protein Binding
Protein Folding
Protein Multimerization

View this publication's entry at the Pubmed website PMID: 26836755
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