10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Molecular determinants of the interaction between HSV-1 glycoprotein D and heparan sulfate

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Literature has well-established the importance of 3- O-sulfation of neuronal cell surface glycan heparan sulfate (HS) to its interaction with herpes simplex virus type 1 glycoprotein D (gD). Previous investigations of gD to its viral receptors HVEM and nectin-1 also highlighted the conformational dynamics of gD’s N- and C-termini, necessary for viral membrane fusion. However, little is known on the structural interactions of gD with HS. Here, we present our findings on this interface from both the glycan and the protein perspective. We used C-terminal and N-terminal gD variants to probe the role of their respective regions in gD/HS binding. The N-terminal truncation mutants (with Δ1-22) demonstrate equivalent or stronger binding to heparin than their intact glycoproteins, indicating that the first 22 amino acids are disposable for heparin binding. Characterization of the conformational differences between C-terminal truncated mutants by sedimentation velocity analytical ultracentrifugation distinguished between the “open” and “closed” conformations of the glycoprotein D, highlighting the region’s modulation of receptor binding. From the glycan perspective, we investigated gD interacting with heparin, heparan sulfate, and other de-sulfated and chemically defined oligosaccharides using surface plasmon resonance and glycan microarray. The results show a strong preference of gD for 6- O-sulfate, with 2- O-sulfation becoming more important in the presence of 6- O-S. Additionally, 3- O-sulfation shifted the chain length preference of gD from longer chain to mid-chain length, reaffirming the sulfation site’s importance to the gD/HS interface. Our results shed new light on the molecular details of one of seven known protein-glycan interactions with 3- O-sulfated heparan sulfate.

          Related collections

          Most cited references73

          • Record: found
          • Abstract: found
          • Article: not found

          Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and lamm equation modeling.

          P. Schuck (2000)
          A new method for the size-distribution analysis of polymers by sedimentation velocity analytical ultracentrifugation is described. It exploits the ability of Lamm equation modeling to discriminate between the spreading of the sedimentation boundary arising from sample heterogeneity and from diffusion. Finite element solutions of the Lamm equation for a large number of discrete noninteracting species are combined with maximum entropy regularization to represent a continuous size-distribution. As in the program CONTIN, the parameter governing the regularization constraint is adjusted by variance analysis to a predefined confidence level. Estimates of the partial specific volume and the frictional ratio of the macromolecules are used to calculate the diffusion coefficients, resulting in relatively high-resolution sedimentation coefficient distributions c(s) or molar mass distributions c(M). It can be applied to interference optical data that exhibit systematic noise components, and it does not require solution or solvent plateaus to be established. More details on the size-distribution can be obtained than from van Holde-Weischet analysis. The sensitivity to the values of the regularization parameter and to the shape parameters is explored with the help of simulated sedimentation data of discrete and continuous model size distributions, and by applications to experimental data of continuous and discrete protein mixtures.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Heparan sulfate proteoglycans.

            Heparan sulfate proteoglycans are found at the cell surface and in the extracellular matrix, where they interact with a plethora of ligands. Over the last decade, new insights have emerged regarding the mechanism and biological significance of these interactions. Here, we discuss changing views on the specificity of protein-heparan sulfate binding and the activity of HSPGs as receptors and coreceptors. Although few in number, heparan sulfate proteoglycans have profound effects at the cellular, tissue, and organismal level.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Order out of chaos: assembly of ligand binding sites in heparan sulfate.

              Virtually every cell type in metazoan organisms produces heparan sulfate. These complex polysaccharides provide docking sites for numerous protein ligands and receptors involved in diverse biological processes, including growth control, signal transduction, cell adhesion, hemostasis, and lipid metabolism. The binding sites consist of relatively small tracts of variably sulfated glucosamine and uronic acid residues in specific arrangements. Their formation occurs in a tissue-specific fashion, generated by the action of a large family of enzymes involved in nucleotide sugar metabolism, polymer formation (glycosyltransferases), and chain processing (sulfotransferases and an epimerase). New insights into the specificity and organization of the biosynthetic apparatus have emerged from genetic studies of cultured cells, nematodes, fruit flies, zebrafish, rodents, and humans. This review covers recent developments in the field and provides a resource for investigators interested in the incredible diversity and specificity of this process.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Mol Biosci
                Front Mol Biosci
                Front. Mol. Biosci.
                Frontiers in Molecular Biosciences
                Frontiers Media S.A.
                2296-889X
                07 November 2022
                2022
                : 9
                : 1043713
                Affiliations
                [1] 1 Center for Biotechnology and Interdisciplinary Studies , Troy, NY, United States
                [2] 2 Chemistry and Chemical Biology Department , Rensselaer Polytechnic Institute , Troy, NY, United States
                [3] 3 Department of Microbiology , School of Dental Medicine , University of Pennsylvania , Philadelphia, PA, United States
                [4] 4 Glycan Therapeutics , Raleigh, NC, United States
                [5] 5 Eshelman School of Pharmacy , University of North Carolina , Chapel Hill, NC, United States
                Author notes

                Edited by: Lei Li, Georgia State University, United States

                Reviewed by: Kyohei Higashi, Tokyo University of Science, Japan

                Junqiang Fang, Shandong University, China

                *Correspondence: Chunyu Wang, wangc5@ 123456rpi.edu

                This article was submittedto Glycoscience, a section of the journal Frontiers in Molecular Biosciences

                Article
                1043713
                10.3389/fmolb.2022.1043713
                9678342
                36419932
                bb1a7334-da60-43d1-8763-231b580e97b3
                Copyright © 2022 Gandy, Canning, Lou, Xia, He, Su, Cairns, Liu, Zhang, Linhardt, Cohen and Wang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 September 2022
                : 26 October 2022
                Funding
                Funded by: National Institutes of Health , doi 10.13039/100000002;
                Award ID: T32AG05764 AG069039 S10OD028523
                Categories
                Molecular Biosciences
                Original Research

                glycoprotein d,herpes,hsv-1,heparin,heparan sulfate
                glycoprotein d, herpes, hsv-1, heparin, heparan sulfate

                Comments

                Comment on this article

                scite_
                0
                0
                0
                0
                Smart Citations
                0
                0
                0
                0
                Citing PublicationsSupportingMentioningContrasting
                View Citations

                See how this article has been cited at scite.ai

                scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

                Similar content175

                Cited by7

                Most referenced authors1,221