Heterodimeric protein entangling motifs: systematic discovery, feature analysis, and topology engineering.

ABSTRACT: Synthesis of nontrivial protein topologies calls for genetically encoded protein entangling motifs, especially those of heterogeneous nature, to achieve structural complexity and functional relevance. Herein, we report the systematic discovery of heterodimeric entangling motifs using criteria like Gauss linking number, buried surface area and terminal distances. These motifs were analyzed to reveal their formation mechanisms (i.e., precursor cleavage, synergistic folding and segment piercing/wrapping) and biological significance (i.e., stability enhancement crucial for executing functions like regulation and catalysis). Six premium motifs were selected for experimental validation. Upon ring closure mediated by orthogonal split inteins, all six motifs led to protein hetero[2]c

SUBMITTER: Xu L 

PROVIDER: S-EPMC12360370 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature