Mutant libraries reveal negative design shielding proteins from supramolecular self-assembly and relocalization in cells.

ABSTRACT: Understanding the molecular consequences of mutations in proteins is essential to map genotypes to phenotypes and interpret the increasing wealth of genomic data. While mutations are known to disrupt protein structure and function, their potential to create new structures and localization phenotypes has not yet been mapped to a sequence space. To map this relationship, we employed two homo-oligomeric protein complexes in which the internal symmetry exacerbates the impact of mutations. We mutagenized three surface residues of each complex and monitored the mutations' effect on localization and assembly phenotypes in yeast cells. While surface mutations are classically viewed as benign, our analysis of several hundred mutants revealed they often trigger three main phenotypes in these protein

SUBMITTER: Garcia Seisdedos H 

PROVIDER: S-EPMC8812688 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature