The ghrelin O-acyltransferase structure reveals a catalytic channel for transmembrane hormone acylation.

ABSTRACT: Integral membrane proteins represent a large and diverse portion of the proteome and are often recalcitrant to purification, impeding studies essential for understanding protein structure and function. By combining co-evolutionary constraints and computational modeling with biochemical validation through site-directed mutagenesis and enzyme activity assays, we demonstrate here a synergistic approach to structurally model purification-resistant topologically complex integral membrane proteins. We report the first structural model of a eukaryotic membrane-bound O-acyltransferase (MBOAT), ghrelin O-acyltransferase (GOAT), which modifies the metabolism-regulating hormone ghrelin. Our structure, generated in the absence of any experimental structural data, revealed an unanticipate

SUBMITTER: Campana MB 

PROVIDER: S-EPMC6768652 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature