The conformational landscape of a serpin N-terminal subdomain facilitates folding and in-cell quality control.

ABSTRACT: Many multi-domain proteins including the serpin family of serine protease inhibitors contain non-sequential domains composed of regions that are far apart in sequence. Because proteins are translated vectorially from N- to C-terminus, such domains pose a particular challenge: how to balance the conformational lability necessary to form productive interactions between early and late translated regions while avoiding aggregation. This balance is mediated by the protein sequence properties and the interactions of the folding protein with the cellular quality control machinery. For serpins, particularly α1-antitrypsin (AAT), mutations often lead to polymer accumulation in cells and consequent disease suggesting that the lability/aggregation balance is especially precarious. Therefore, we inves

SUBMITTER: Kaur U 

PROVIDER: S-EPMC10168285 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature