Examination of glycosaminoglycan binding sites on the XCL1 dimer

Authors
Fox, Jamie C.
Tyler, Robert C.
Peterson, Francis C.
Dyer, Douglas P.
Zhang, Fuming
Linhardt, Robert J.
Handel, Tracy M.
Volkman, Brian F.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2016-03-01
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Full Citation
Examination of glycosaminoglycan binding sites on the XCL1 dimer, J. C. Fox, R. C. Tyler, F. C. Peterson, D. P. Dyer, F. Zhang, R. J. Linhardt, T. M. Handel, B. F. Volkman, Biochemistry, 55, 1214–1225, 2016.
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.
Description
Biochemistry, 55, 1214–1225
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
American Chemical Society (ACS)
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Biochemistry
https://harc.rpi.edu/
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A full text version is available in DSpace@RPI