title: Molecular insights into prolyl and lysyl hydroxylation of fibrillar collagens in health and disease.
abstract: Collagen is a macromolecule that has versatile roles in physiology, ranging from structural support to mediating cell signaling. Formation of mature collagen fibrils out of procollagen α-chains requires a variety of enzymes and chaperones in a complex process spanning both intracellular and extracellular post-translational modifications. These processes include modifications of amino acids, folding of procollagen α-chains into a triple-helical configuration and subsequent stabilization, facilitation of transportation out of the cell, cleavage of propeptides, aggregation, cross-link formation, and finally the formation of mature fibrils. Disruption of any of the proteins involved in these biosynthesis steps potentially result in a variety of connective tissue diseases because of a destabilized extracellular matrix. In this review, we give a revised overview of the enzymes and chaperones currently known to be relevant to the conversion of lysine and proline into hydroxyproline and hydroxylysine, respectively, and the O-glycosylation of hydroxylysine and give insights into the consequences when these steps are disrupted.
authors.affiliation: a MATRIX Research Group, Department of Pathology and Medical Biology , University Medical Center Groningen, University of Groningen , Groningen , the Netherlands.
authors.forename: Rutger A F
authors.initials: RA
authors.lastname: Gjaltema
authors.affiliation: a MATRIX Research Group, Department of Pathology and Medical Biology , University Medical Center Groningen, University of Groningen , Groningen , the Netherlands.
authors.forename: Ruud A
authors.initials: RA
authors.lastname: Bank
mesh_terms: D000818:Animals; D001176:Arthrogryposis / Q000378:metabolism / Q000473:pathology; D003240:Connective Tissue Diseases / Q000378:metabolism / Q000473:pathology; D004535:Ehlers-Danlos Syndrome / Q000378:metabolism / Q000473:pathology; D024022:Fibrillar Collagens / Q000032:analysis / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D006900:Hydroxylation; D006901:Hydroxylysine / Q000032:analysis / Q000378:metabolism; D006909:Hydroxyproline / Q000032:analysis / Q000378:metabolism; D008239:Lysine / Q000032:analysis / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000378:metabolism / Q000473:pathology; D011392:Proline / Q000032:analysis / Q000378:metabolism; D017510:Protein Folding
chemical_list: D024022:Fibrillar Collagens; D006901:Hydroxylysine; D011392:Proline; D008239:Lysine; D006909:Hydroxyproline
keywords: Bruck syndrome; Collagen; Ehlers–Danlos syndrome; connective tissue disorders; fibrosis; lysyl hydroxylation; osteogenesis imperfecta; prolyl hydroxylation