Chiral inversion mutagenesis identifies geometrically constrained residues within self-associating low-complexity domains.

ABSTRACT: Many protein low-complexity domains (LCDs) reversibly self-associate to enable cellular function, yet fundamental questions remain regarding how polypeptide chemical and structural features beyond side chain identity contribute to LCD-LCD interactions. For instance, the folds adopted by globular proteins emerge from constraints enforced by homo-chirality of genetically-encoded polypeptides. However, it remains unclear to what extent similar geometric constraints apply to LCD self-association. Herein, we use protein total- and semi-synthesis to probe the contribution of C^α stereochemistry to LCD self-association with synthetic Chiral Inversion Mutagenesis (ChIM). By introducing targeted L-to-D amino acid inversions, ChIM identifies C^α stereocenters under geometric cons

SUBMITTER: Beckner RL 

PROVIDER: S-EPMC12724595 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature