title: Hydroxyproline Ring Pucker Causes Frustration of Helix Parameters in the Collagen Triple Helix.
abstract: Collagens, the most abundant proteins in mammals, are defined by their triple-helical structures and distinctive Gly-Xaa-Yaa repeating sequence, where Xaa is often proline and Yaa, hydroxyproline (Hyp/O). It is known that hydroxyproline in the Yaa position stabilises the triple helix, and that lack of proline hydroxylation in vivo leads to dysfunctional collagen extracellular matrix assembly, due to a range of factors such as a change in hydration properties. In addition, we note that in model peptides, when Yaa is unmodified proline, the Xaa proline has a strong propensity to adopt an endo ring conformation, whilst when Yaa is hydroxyproline, the Xaa proline adopts a range of endo and exo conformations. Here we use a combination of solid-state NMR spectroscopy and potential energy landscape modelling of synthetic triple-helical collagen peptides to understand this effect. We show that hydroxylation of the Yaa proline causes the Xaa proline ring conformation to become metastable, which in turn confers flexibility on the triple helix.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: W Ying
authors.initials: WY
authors.lastname: Chow
authors.affiliation: Department of Biochemistry, University of Cambridge, Downing Site, Cambridge CB2 1QW, UK.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bihan
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Forman
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Slatter
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: David G
authors.initials: DG
authors.lastname: Reid
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wales
authors.affiliation: Department of Biochemistry, University of Cambridge, Downing Site, Cambridge CB2 1QW, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Farndale
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Melinda J
authors.initials: MJ
authors.lastname: Duer
mesh_terms: D003094:Collagen / Q000737:chemistry*; D006900:Hydroxylation; D006909:Hydroxyproline / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline