title: The structural motifs for substrate binding and dimerization of the α subunit of collagen prolyl 4-hydroxylase.
abstract: Collagen prolyl 4-hydroxylase (C-P4H) catalyzes the proline hydroxylation of procollagen, an essential modification in the maturation of collagens. C-P4H consists of two catalytic α subunits and two protein disulfide isomerase β subunits. The assembly of these subunits is unknown. The α subunit contains an N domain (1-143), a peptide-substrate-binding-domain (PSB, 144-244) and a catalytic domain (245-517). Here, we report the dimeric structure of the N-terminal region (1-244) of the α subunit. It is shown that the N domain has an important role in the assembly of the C-P4H tetramer, by forming an extended four-helix bundle that includes an antiparallel coiled-coil dimerization motif between the two α subunits. Complexes of this construct with a C-P4H inhibitor and substrate show the mode of peptide-binding to the PSB domain. Both peptides adopt a poly-(L)-proline-type-II helix conformation and bind in a curved, asymmetric groove lined by conserved tyrosines and an Arg-Asp salt bridge.
authors.affiliation: Biocenter Oulu and Department of Biochemistry, University of Oulu, P.O. Box 3000, FIN-90014 Oulu, Finland.
authors.forename: Jothi
authors.initials: J
authors.lastname: Anantharajan
authors.forename: M Kristian
authors.initials: MK
authors.lastname: Koski
authors.forename: Petri
authors.initials: P
authors.lastname: Kursula
authors.forename: Reija
authors.initials: R
authors.lastname: Hieta
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bergmann
authors.forename: Johanna
authors.initials: J
authors.lastname: Myllyharju
authors.forename: Rik K
authors.initials: RK
authors.lastname: Wierenga
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011393:Procollagen-Proline Dioxygenase / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D010455:Peptides; D021122:Protein Subunits; D011393:Procollagen-Proline Dioxygenase