Structure of transmembrane prolyl 4-hydroxylase reveals unique organization of EF and dioxygenase domains.

ABSTRACT: Prolyl 4-hydroxylases (P4Hs) catalyze post-translational hydroxylation of peptidyl proline residues. In addition to collagen P4Hs and hypoxia-inducible factor P4Hs, a third P4H-the poorly characterized endoplasmic reticulum-localized transmembrane prolyl 4-hydroxylase (P4H-TM)-is found in animals. P4H-TM variants are associated with the familiar neurological HIDEA syndrome, but how these variants might contribute to disease is unknown. Here, we explored this question in a structural and functional analysis of soluble human P4H-TM. The crystal structure revealed an EF domain with two Ca²⁺-binding motifs inserted within the catalytic domain. A substrate-binding groove was formed between the EF domain and the conserved core of the catalytic domain. The proximity of the EF domain to

SUBMITTER: Myllykoski M 

PROVIDER: S-EPMC7948501 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature