TUTCRIS - Tampereen teknillinen yliopisto

TUTCRIS

The structural motifs for substrate binding and dimerization of the α subunit of collagen prolyl 4-hydroxylase

Tutkimustuotosvertaisarvioitu

Yksityiskohdat

AlkuperäiskieliEnglanti
Sivut2107-2118
Sivumäärä12
JulkaisuStructure
Vuosikerta21
Numero12
DOI - pysyväislinkit
TilaJulkaistu - 3 joulukuuta 2013
OKM-julkaisutyyppiA1 Alkuperäisartikkeli

Tiivistelmä

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.

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