Allosteric Communication across STAT3 Domains Associated with STAT3 Function and Disease-Causing Mutation.

ABSTRACT: STAT3 is a member of STAT (signal transducer and activator of transcription) transcription activators. Aberration in STAT3 activity due to constitutive activation or mutations leads to diseases such as cancer and hyper-immunoglobulin E syndrome (HIES). STAT3 contains several structured domains including the Src homology 2 domain (SH2), linker domain (LD), DNA-binding domain (DBD) and the coiled-coil domain. Here we report the discovery of inter-domain allosteric communications in STAT3 from studies using nuclear magnetic resonance (NMR) and other methods. We found that pTyr-peptide interactions with SH2 cause structural and dynamics changes in LD and DBD. The inter-domain allosteric effect is likely mediated by the flexibility in the hydrophobic core. In addition, a mutation in LD found in

SUBMITTER: Namanja AT 

PROVIDER: S-EPMC4767637 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature