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

Date

02/03/2016

Pubmed ID

26836755

Pubmed Central ID

PMC4775286

DOI

10.1021/acs.biochem.5b01329

Scopus ID

2-s2.0-84959421606   10 Citations

Abstract

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

Authors

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
Glycosaminoglycans
HIV Infections
HIV-1
Heparin
Heparitin Sulfate
Humans
Models, Molecular
Point Mutation
Protein Binding
Protein Folding
Protein Multimerization
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab