Projects per year
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 angstrom), a putative transcriptional regulator of key arabinosyltransferases (EmbC, -A, and -B), and an endogenous substrate of the Ser/Thrkinase 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 angstrom) 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.
Original language | English |
---|---|
Pages (from-to) | 2558-2563 |
Number of pages | 6 |
Journal | National Academy of Sciences. Proceedings |
Volume | 103 |
Issue number | 8 |
DOIs | |
Publication status | Published - 6 Feb 2006 |
Keywords
- transcriptional regulator
- ethambutol
- arabinosyltransferase
- x-ray crystallography
- PknH
Fingerprint
Dive into the research topics of 'Molecular structure of EmbR, a response element of Ser/Thr kinase signaling in Mycobacterium tuberculosis'. Together they form a unique fingerprint.Projects
- 1 Finished
-
MAGPIE Project: The Structure and Assembly of the Mycobacterial Cell Envelope
Besra, D., Lammas, T. & Minnikin, D.
1/02/06 → 31/01/11
Project: Research Councils