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

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@article{a81221c5c92d427e9a9f150d3311e30d,
title = "Molecular structure of EmbR, a response element of Ser/Thr kinase signaling in Mycobacterium tuberculosis",
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.",
keywords = "transcriptional regulator, ethambutol, arabinosyltransferase, x-ray crystallography, PknH",
author = "Luke Alderwick and V Molle and L Kremer and AJ Cuzzone and Timothy Dafforn and Gurdyal Besra and Klaus Futterer",
year = "2006",
month = feb,
day = "6",
doi = "10.1073/pnas.0507766103",
language = "English",
volume = "103",
pages = "2558--2563",
journal = "National Academy of Sciences. Proceedings",
issn = "1091-6490",
publisher = "National Academy of Sciences",
number = "8",

}

RIS

TY - JOUR

T1 - Molecular structure of EmbR, a response element of Ser/Thr kinase signaling in Mycobacterium tuberculosis

AU - Alderwick, Luke

AU - Molle, V

AU - Kremer, L

AU - Cuzzone, AJ

AU - Dafforn, Timothy

AU - Besra, Gurdyal

AU - Futterer, Klaus

PY - 2006/2/6

Y1 - 2006/2/6

N2 - 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.

AB - 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.

KW - transcriptional regulator

KW - ethambutol

KW - arabinosyltransferase

KW - x-ray crystallography

KW - PknH

UR - http://www.scopus.com/inward/record.url?scp=33644500423&partnerID=8YFLogxK

U2 - 10.1073/pnas.0507766103

DO - 10.1073/pnas.0507766103

M3 - Article

VL - 103

SP - 2558

EP - 2563

JO - National Academy of Sciences. Proceedings

JF - National Academy of Sciences. Proceedings

SN - 1091-6490

IS - 8

ER -