HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease

Heparan sulfate is a ubiquitous, variably sulfated interactive glycosaminoglycan that consists of repeating disaccharides of glucuronic acid and glucosamine that are subject to a number of modifications (acetylation, de-acetylation, epimerization, sulfation). Variable heparan sulfate chain lengths a...

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Published in	International journal of molecular sciences Vol. 24; no. 2; p. 1148
Main Authors	Hayes, Anthony J, Melrose, James
Format	Journal Article
Language	English
Published	Switzerland MDPI AG 06.01.2023 MDPI
Subjects	Acetylation Artificial Intelligence Carbohydrates Cell differentiation Cell proliferation cell/matrix interaction Chains Chemokine receptors Chemokines Computer applications Disaccharides Drug development Enzymes Gene expression Genomes Glucosamine Glycosaminoglycans Glycosaminoglycans - metabolism Growth factors Heparan sulfate heparan sulfate proteoglycan Heparitin Sulfate - metabolism Homeostasis Immunoregulation Information storage Ligands Molecular docking Molecular Docking Simulation Neural networks Oligosaccharides Physiology Proteins Proteoglycans Proteoglycans - metabolism Review Stem cells Sulfation sulfation motif tissue homeostasis Tumors Wound healing cell/matrix interaction heparan sulfate sulfation motif heparan sulfate proteoglycan tissue homeostasis
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Abstract	Heparan sulfate is a ubiquitous, variably sulfated interactive glycosaminoglycan that consists of repeating disaccharides of glucuronic acid and glucosamine that are subject to a number of modifications (acetylation, de-acetylation, epimerization, sulfation). Variable heparan sulfate chain lengths and sequences within the heparan sulfate chains provide structural diversity generating interactive oligosaccharide binding motifs with a diverse range of extracellular ligands and cellular receptors providing instructional cues over cellular behaviour and tissue homeostasis through the regulation of essential physiological processes in development, health, and disease. heparan sulfate and heparan sulfate-PGs are integral components of the specialized glycocalyx surrounding cells. Heparan sulfate is the most heterogeneous glycosaminoglycan, in terms of its sequence and biosynthetic modifications making it a difficult molecule to fully characterize, multiple ligands also make an elucidation of heparan sulfate functional properties complicated. Spatio-temporal presentation of heparan sulfate sulfate groups is an important functional determinant in tissue development and in cellular control of wound healing and extracellular remodelling in pathological tissues. The regulatory properties of heparan sulfate are mediated via interactions with chemokines, chemokine receptors, growth factors and morphogens in cell proliferation, differentiation, development, tissue remodelling, wound healing, immune regulation, inflammation, and tumour development. A greater understanding of these HS interactive processes will improve therapeutic procedures and prognoses. Advances in glycosaminoglycan synthesis and sequencing, computational analytical carbohydrate algorithms and advanced software for the evaluation of molecular docking of heparan sulfate with its molecular partners are now available. These advanced analytic techniques and artificial intelligence offer predictive capability in the elucidation of heparan sulfate conformational effects on heparan sulfate-ligand interactions significantly aiding heparan sulfate therapeutics development.
AbstractList	Heparan sulfate is a ubiquitous, variably sulfated interactive glycosaminoglycan that consists of repeating disaccharides of glucuronic acid and glucosamine that are subject to a number of modifications (acetylation, de-acetylation, epimerization, sulfation). Variable heparan sulfate chain lengths and sequences within the heparan sulfate chains provide structural diversity generating interactive oligosaccharide binding motifs with a diverse range of extracellular ligands and cellular receptors providing instructional cues over cellular behaviour and tissue homeostasis through the regulation of essential physiological processes in development, health, and disease. heparan sulfate and heparan sulfate-PGs are integral components of the specialized glycocalyx surrounding cells. Heparan sulfate is the most heterogeneous glycosaminoglycan, in terms of its sequence and biosynthetic modifications making it a difficult molecule to fully characterize, multiple ligands also make an elucidation of heparan sulfate functional properties complicated. Spatio-temporal presentation of heparan sulfate sulfate groups is an important functional determinant in tissue development and in cellular control of wound healing and extracellular remodelling in pathological tissues. The regulatory properties of heparan sulfate are mediated via interactions with chemokines, chemokine receptors, growth factors and morphogens in cell proliferation, differentiation, development, tissue remodelling, wound healing, immune regulation, inflammation, and tumour development. A greater understanding of these HS interactive processes will improve therapeutic procedures and prognoses. Advances in glycosaminoglycan synthesis and sequencing, computational analytical carbohydrate algorithms and advanced software for the evaluation of molecular docking of heparan sulfate with its molecular partners are now available. These advanced analytic techniques and artificial intelligence offer predictive capability in the elucidation of heparan sulfate conformational effects on heparan sulfate-ligand interactions significantly aiding heparan sulfate therapeutics development.
Author	Hayes, Anthony J Melrose, James
AuthorAffiliation	3 Raymond Purves Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia 2 Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia 1 Bioimaging Research Hub, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK 4 Northern Sydney Local Health District, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
AuthorAffiliation_xml	– name: 4 Northern Sydney Local Health District, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia – name: 1 Bioimaging Research Hub, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK – name: 2 Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia – name: 3 Raymond Purves Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
Author_xml	– sequence: 1 givenname: Anthony J orcidid: 0000-0002-2918-3723 surname: Hayes fullname: Hayes, Anthony J organization: Bioimaging Research Hub, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK – sequence: 2 givenname: James orcidid: 0000-0001-9237-0524 surname: Melrose fullname: Melrose, James organization: Northern Sydney Local Health District, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/36674659$$D View this record in MEDLINE/PubMed
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CitedBy_id	crossref_primary_10_1111_febs_17107 crossref_primary_10_4103_1673_5374_377606 crossref_primary_10_1152_ajpcell_00683_2023 crossref_primary_10_14336_AD_2023_0131 crossref_primary_10_3390_ijms241814101 crossref_primary_10_1016_j_carbpol_2024_122106 crossref_primary_10_1128_jvi_00832_23 crossref_primary_10_1002_pgr2_21
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Keywords	cell/matrix interaction heparan sulfate sulfation motif heparan sulfate proteoglycan tissue homeostasis
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License	https://creativecommons.org/licenses/by/4.0 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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SubjectTerms	Acetylation Artificial Intelligence Carbohydrates Cell differentiation Cell proliferation cell/matrix interaction Chains Chemokine receptors Chemokines Computer applications Disaccharides Drug development Enzymes Gene expression Genomes Glucosamine Glycosaminoglycans Glycosaminoglycans - metabolism Growth factors Heparan sulfate heparan sulfate proteoglycan Heparitin Sulfate - metabolism Homeostasis Immunoregulation Information storage Ligands Molecular docking Molecular Docking Simulation Neural networks Oligosaccharides Physiology Proteins Proteoglycans Proteoglycans - metabolism Review Stem cells Sulfation sulfation motif tissue homeostasis Tumors Wound healing
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Title	HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease
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