
TetRアロステリーの二つのドメインの熱力学モデルは、アロステリーホットスポットの広範な分布や、致死変異の機能回復といった興味深い観察結果を説明できる。


coremsg

New experimental findings continue to challenge our understanding of protein allostery. Recent deep mutational scanning study showed that allosteric hotspots in the tetracycline repressor (TetR) and its homologous transcriptional factors are broadly distributed rather than spanning well-defined structural pathways as often assumed. Moreover, hotspot mutation-induced allostery loss was rescued by distributed additional mutations in a degenerate fashion. Here, we develop a two-domain thermodynamic model for TetR, which readily rationalizes these intriguing observations. The model accurately captures the in vivo activities of various mutants with changes in physically transparent parameters, allowing the data-based quantification of mutational effects using statistical inference. Our analysis reveals the intrinsic connection of intra- and inter-domain properties for allosteric regulation and illustrate epistatic interactions that are consistent with structural features of the protein. The insights gained from this study into the nature of two-domain allostery are expected to have broader implications for other multidomain allosteric proteins.

### Competing Interest Statement

The authors have declared no competing interest.

A parametrized two-domain thermodynamic model explains diverse mutational effects on protein allostery

tetrの二つのドメインの熱力学モデルが多様な変異の蛋白質アロステリーへの影響を説明する


TetRの二つのドメインの熱力学モデルが多様な変異の蛋白質アロステリーへの影響を説明する
