Allosteric Autoinhibition Pathway in Transcription Factor ERG: Dynamics Network and Mutant Experimental Evaluations.

ABSTRACT: Allosteric autoinhibition exists in many transcription factors. The ERG proteins exhibit autoinhibition on DNA binding by the C-terminal and N-terminal inhibitory domains (CID and NID). However, the autoinhibition mechanism and allosteric pathway of ERG are unknown. In this study we intend to elucidate the residue-level allosteric mechanism and pathway via a combined approach of computational and experimental analyses. Specifically computational residue-level fluctuation correlation data was analyzed to reveal detailed dynamics signatures in the allosteric autoinhibition process. A hypothesis of "NID/CID binding induced allostery" is proposed to link similar structures and different protein functions, which is subsequently validated by perturbation and mutation analyses in both computation

SUBMITTER: Ye W 

PROVIDER: S-EPMC5730271 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature