Dissecting the Determinants of Domain Insertion Tolerance and Allostery in Proteins.

ABSTRACT: Domain insertion engineering is a promising approach to recombine the functions of evolutionarily unrelated proteins. Insertion of light-switchable receptor domains into a selected effector protein, for instance, can yield allosteric effectors with light-dependent activity. However, the parameters that determine domain insertion tolerance and allostery are poorly understood. Here, an unbiased screen is used to systematically assess the domain insertion permissibility of several evolutionary unrelated proteins. Training machine learning models on the resulting data allow to dissect features informative for domain insertion tolerance and revealed sequence conservation statistics as the strongest indicators of suitable insertion sites. Finally, extending the experimental pipeline toward the i

SUBMITTER: Mathony J 

PROVIDER: S-EPMC10558690 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature