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Publication Abstract from PubMed

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 alpha subunits and two protein disulfide isomerase beta subunits. The assembly of these subunits is unknown. The alpha 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 alpha 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 alpha 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.

The Structural Motifs for Substrate Binding and Dimerization of the alpha Subunit of Collagen Prolyl 4-Hydroxylase.,Anantharajan J, Koski MK, Kursula P, Hieta R, Bergmann U, Myllyharju J, Wierenga RK Structure. 2013 Oct 23. pii: S0969-2126(13)00355-9. doi:, 10.1016/j.str.2013.09.005. PMID:24207127^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.