Molecular structure of EmbR, a response element of Ser/Thr kinase signaling in Mycobacterium tuberculosis

Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2558-63. doi: 10.1073/pnas.0507766103. Epub 2006 Feb 13.

Abstract

Ser/Thr phosphorylation has emerged as a critical regulatory mechanism in a number of bacteria, including Mycobacterium tuberculosis. This problematic pathogen encodes 11 eukaryotic-like Ser/Thr kinases, yet few substrates or signaling targets have been characterized. Here, we report the structure of EmbR (2.0 A), a putative transcriptional regulator of key arabinosyltransferases (EmbC, -A, and -B), and an endogenous substrate of the Ser/Thr-kinase PknH. EmbR presents a unique domain architecture: the N-terminal winged-helix DNA-binding domain forms an extensive interface with the all-helical central bacterial transcriptional activation domain and is positioned adjacent to the regulatory C-terminal forkhead-associated (FHA) domain, which mediates binding to a Thr-phosphorylated site in PknH. The structure in complex with a phospho-peptide (1.9 A) reveals a conserved mode of phospho-threonine recognition by the FHA domain and evidence for specific recognition of the cognate kinase. The present structures suggest hypotheses as to how EmbR might propagate the phospho-relay signal from its cognate kinase, while serving as a template for the structurally uncharacterized Streptomyces antibiotic regulatory protein family of transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / metabolism*
  • Peptides / chemistry
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Structure, Tertiary
  • Response Elements
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism
  • X-Ray Diffraction

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • Peptides
  • Transcription Factors
  • Protein Serine-Threonine Kinases

Associated data

  • PDB/2FEZ
  • PDB/2FF4