7ZSC

Crystal structure of the heterodimeric human C-P4H-II with truncated alpha subunit (C-P4H-II delta281)

Summary for 7ZSC

• Entry DOI: 10.2210/pdb7zsc/pdb
• Descriptor: Prolyl 4-hydroxylase subunit alpha-2, Protein disulfide-isomerase, SULFATE ION (3 entities in total)
• Functional Keywords: collagen synthesis, pdi, dsbh fold, thioredoxin, dioxygenase, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 171764.48

Authors

Lebedev, A.,Koski, M.K.,Wierenga, R.K.,Murthy, A.V.,Sulu, R. (deposition date: 2022-05-06, release date: 2022-11-09, Last modification date: 2024-11-13)

Primary citation

Murthy, A.V.,Sulu, R.,Lebedev, A.,Salo, A.M.,Korhonen, K.,Venkatesan, R.,Tu, H.,Bergmann, U.,Janis, J.,Laitaoja, M.,Ruddock, L.W.,Myllyharju, J.,Koski, M.K.,Wierenga, R.K.
Crystal structure of the collagen prolyl 4-hydroxylase (C-P4H) catalytic domain complexed with PDI: Toward a model of the C-P4H alpha 2 beta 2 tetramer.
J.Biol.Chem., 298:102614-102614, 2022

PubMed Abstract: Collagen prolyl 4-hydroxylases (C-P4H) are αβ tetramers, which catalyze the prolyl 4-hydroxylation of procollagen, allowing for the formation of the stable triple-helical collagen structure in the endoplasmic reticulum. The C-P4H α-subunit provides the N-terminal dimerization domain, the middle peptide-substrate-binding (PSB) domain, and the C-terminal catalytic (CAT) domain, whereas the β-subunit is identical to the enzyme protein disulfide isomerase (PDI). The structure of the N-terminal part of the α-subunit (N-terminal region and PSB domain) is known, but the structures of the PSB-CAT linker region and the CAT domain as well as its mode of assembly with the β/PDI subunit, are unknown. Here, we report the crystal structure of the CAT domain of human C-P4H-II complexed with the intact β/PDI subunit, at 3.8 Å resolution. The CAT domain interacts with the a, b', and a' domains of the β/PDI subunit, such that the CAT active site is facing bulk solvent. The structure also shows that the C-P4H-II CAT domain has a unique N-terminal extension, consisting of α-helices and a β-strand, which is the edge strand of its major antiparallel β-sheet. This extra region of the CAT domain interacts tightly with the β/PDI subunit, showing that the CAT-PDI interface includes an intersubunit disulfide bridge with the a' domain and tight hydrophobic interactions with the b' domain. Using this new information, the structure of the mature C-P4H-II αβ tetramer is predicted. The model suggests that the CAT active-site properties are modulated by α-helices of the N-terminal dimerization domains of both subunits of the α-dimer.

PubMed: 36265586
DOI: 10.1016/j.jbc.2022.102614

Experimental method

X-RAY DIFFRACTION (3.85 Å)