
두 영역 열역학 모델은 TetR 단백질의 알로스테리 조절에 대한 다양한 돌연변이 효과를 잘 설명할 수 있다.


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-단백질의-다양한-돌연변이-효과를-설명하는-매개변수화된-두-영역-열역학-모델


TetR 단백질의 다양한 돌연변이 효과를 설명하는 매개변수화된 두 영역 열역학 모델
