Trimethyllysine Reader Proteins Exhibit Widespread Charge-Agnostic Binding via Different Mechanisms to Cationic and Neutral Ligands.

ABSTRACT: In the last 40 years, cation-π interactions have become part of the lexicon of noncovalent forces that drive protein binding. Indeed, tetraalkylammoniums are universally bound by aromatic cages in proteins, suggesting that cation-π interactions are a privileged mechanism for binding these ligands. A prominent example is the recognition of histone trimethyllysine (Kme3) by the conserved aromatic cage of reader proteins, dictating gene expression. However, two proteins have recently been suggested as possible exceptions to the conventional understanding of tetraalkylammonium recognition. To broadly interrogate the role of cation-π interactions in protein binding interactions, we report the first large-scale comparative evaluation of reader proteins for a neutral Kme3 isostere, experimental a

SUBMITTER: Travis CR 

PROVIDER: S-EPMC11140585 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature