Nascent chains can form co-translational folding intermediates that promote post-translational folding outcomes in a disease-causing protein.

ABSTRACT: During biosynthesis, proteins can begin folding co-translationally to acquire their biologically-active structures. Folding, however, is an imperfect process and in many cases misfolding results in disease. Less is understood of how misfolding begins during biosynthesis. The human protein, alpha-1-antitrypsin (AAT) folds under kinetic control via a folding intermediate; its pathological variants readily form self-associated polymers at the site of synthesis, leading to alpha-1-antitrypsin deficiency. We observe that AAT nascent polypeptides stall during their biosynthesis, resulting in full-length nascent chains that remain bound to ribosome, forming a persistent ribosome-nascent chain complex (RNC) prior to release. We analyse the structure of these RNCs, which reveals compacted, partiall

SUBMITTER: Plessa E 

PROVIDER: S-EPMC8576036 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature