The affinity of Ets-1 for DNA is modulated by phosphorylation through transient interactions of an unstructured region.

ABSTRACT: Binding of the transcription factor Ets-1 to DNA is allosterically regulated by a serine-rich region (SRR) that modulates the dynamic character of the adjacent structured DNA-binding ETS domain and its flanking autoinhibitory elements. Multi-site phosphorylation of the flexible SRR in response to Ca(2+) signaling mediates variable regulation of Ets-1 DNA-binding affinity. In this study, we further investigated the mechanism of this regulation. First, thermal and urea denaturation experiments demonstrated that phosphorylation of the predominantly unstructured SRR imparts enhanced thermodynamic stability on the well-folded ETS domain and its inhibitory module. We next identified a minimal fragment (residues 279-440) that exhibits both enhanced autoinhibition of Ets-1 DNA-binding and alloster

SUBMITTER: Lee GM 

PROVIDER: S-EPMC4808631 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature