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Crystal structure of the VapBC-15 complex from Mycobacterium tuberculosis reveals a two-metal ion dependent PIN-domain ribonuclease and a variable mode of toxin-antitoxin assembly

Standard

Crystal structure of the VapBC-15 complex from Mycobacterium tuberculosis reveals a two-metal ion dependent PIN-domain ribonuclease and a variable mode of toxin-antitoxin assembly. / Das, Uddipan; Pogenberg, Vivian; Subhramanyam, Udaya Kumar Tiruttani; Wilmanns, Matthias; Gourinath, Samudrala; Srinivasan, Alagiri.

in: J STRUCT BIOL, Jahrgang 188, Nr. 3, 12.2014, S. 249-58.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Das, U, Pogenberg, V, Subhramanyam, UKT, Wilmanns, M, Gourinath, S & Srinivasan, A 2014, 'Crystal structure of the VapBC-15 complex from Mycobacterium tuberculosis reveals a two-metal ion dependent PIN-domain ribonuclease and a variable mode of toxin-antitoxin assembly', J STRUCT BIOL, Jg. 188, Nr. 3, S. 249-58. https://doi.org/10.1016/j.jsb.2014.10.002

APA

Das, U., Pogenberg, V., Subhramanyam, U. K. T., Wilmanns, M., Gourinath, S., & Srinivasan, A. (2014). Crystal structure of the VapBC-15 complex from Mycobacterium tuberculosis reveals a two-metal ion dependent PIN-domain ribonuclease and a variable mode of toxin-antitoxin assembly. J STRUCT BIOL, 188(3), 249-58. https://doi.org/10.1016/j.jsb.2014.10.002

Vancouver

Das U, Pogenberg V, Subhramanyam UKT, Wilmanns M, Gourinath S, Srinivasan A. Crystal structure of the VapBC-15 complex from Mycobacterium tuberculosis reveals a two-metal ion dependent PIN-domain ribonuclease and a variable mode of toxin-antitoxin assembly. J STRUCT BIOL. 2014 Dez;188(3):249-58. https://doi.org/10.1016/j.jsb.2014.10.002

Bibtex

@article{44ff620c4e884118b94fe0177a481595,
title = "Crystal structure of the VapBC-15 complex from Mycobacterium tuberculosis reveals a two-metal ion dependent PIN-domain ribonuclease and a variable mode of toxin-antitoxin assembly",
abstract = "Although PIN (PilT N-terminal)-domain proteins are known to have ribonuclease activity, their specific mechanism of action remains unknown. VapCs form a family of ribonucleases that possess a PIN-domain assembly and are known as toxins. The activities of VapCs are impaired by VapB antitoxins. Here we present the crystal structure of the VapBC-15 toxin-antitoxin complex from Mycobacterium tuberculosis determined to 2.1{\AA} resolution. The VapB-15 and VapC-15 components assemble into one heterotetramer (VapB2C2) and two heterotrimers (VapBC2) in each asymmetric unit of the crystal. The active site of VapC-15 toxin consists of a cluster of acidic amino acid residues and two divalent metal ions, forming a well organised ribonuclease active site. The distribution of the catalytic-site residues of the VapC-15 toxin is similar to that of T4 RNase H and of Methanococcus jannaschii FEN-1, providing strong evidence that these three proteins share a similar mechanism of activity. The presence of both VapB2C2 and VapBC2 emphasizes the fact that the same antitoxin can bind the toxin in 1:1 and 1:2 ratios. The crystal structure determination of the VapBC-15 complex reveals for the first time a PIN-domain ribonuclease protein that shows two metal ions at the active site and a variable mode of toxin-antitoxin assembly. The structure further shows that VapB-15 antitoxin binds to the same groove meant for the binding of putative substrate (RNA), resulting in the inhibition of VapC-15's toxicity. ",
keywords = "Antitoxins/metabolism, Bacterial Proteins/metabolism, Bacterial Toxins/metabolism, DNA-Binding Proteins/metabolism, Membrane Glycoproteins/metabolism, Models, Molecular, Mycobacterium tuberculosis/metabolism, Protein Structure, Tertiary, Ribonucleases/metabolism, X-Ray Diffraction",
author = "Uddipan Das and Vivian Pogenberg and Subhramanyam, {Udaya Kumar Tiruttani} and Matthias Wilmanns and Samudrala Gourinath and Alagiri Srinivasan",
note = "Copyright {\textcopyright} 2014 Elsevier Inc. All rights reserved.",
year = "2014",
month = dec,
doi = "10.1016/j.jsb.2014.10.002",
language = "English",
volume = "188",
pages = "249--58",
journal = "J STRUCT BIOL",
issn = "1047-8477",
publisher = "Academic Press Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Crystal structure of the VapBC-15 complex from Mycobacterium tuberculosis reveals a two-metal ion dependent PIN-domain ribonuclease and a variable mode of toxin-antitoxin assembly

AU - Das, Uddipan

AU - Pogenberg, Vivian

AU - Subhramanyam, Udaya Kumar Tiruttani

AU - Wilmanns, Matthias

AU - Gourinath, Samudrala

AU - Srinivasan, Alagiri

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/12

Y1 - 2014/12

N2 - Although PIN (PilT N-terminal)-domain proteins are known to have ribonuclease activity, their specific mechanism of action remains unknown. VapCs form a family of ribonucleases that possess a PIN-domain assembly and are known as toxins. The activities of VapCs are impaired by VapB antitoxins. Here we present the crystal structure of the VapBC-15 toxin-antitoxin complex from Mycobacterium tuberculosis determined to 2.1Å resolution. The VapB-15 and VapC-15 components assemble into one heterotetramer (VapB2C2) and two heterotrimers (VapBC2) in each asymmetric unit of the crystal. The active site of VapC-15 toxin consists of a cluster of acidic amino acid residues and two divalent metal ions, forming a well organised ribonuclease active site. The distribution of the catalytic-site residues of the VapC-15 toxin is similar to that of T4 RNase H and of Methanococcus jannaschii FEN-1, providing strong evidence that these three proteins share a similar mechanism of activity. The presence of both VapB2C2 and VapBC2 emphasizes the fact that the same antitoxin can bind the toxin in 1:1 and 1:2 ratios. The crystal structure determination of the VapBC-15 complex reveals for the first time a PIN-domain ribonuclease protein that shows two metal ions at the active site and a variable mode of toxin-antitoxin assembly. The structure further shows that VapB-15 antitoxin binds to the same groove meant for the binding of putative substrate (RNA), resulting in the inhibition of VapC-15's toxicity.

AB - Although PIN (PilT N-terminal)-domain proteins are known to have ribonuclease activity, their specific mechanism of action remains unknown. VapCs form a family of ribonucleases that possess a PIN-domain assembly and are known as toxins. The activities of VapCs are impaired by VapB antitoxins. Here we present the crystal structure of the VapBC-15 toxin-antitoxin complex from Mycobacterium tuberculosis determined to 2.1Å resolution. The VapB-15 and VapC-15 components assemble into one heterotetramer (VapB2C2) and two heterotrimers (VapBC2) in each asymmetric unit of the crystal. The active site of VapC-15 toxin consists of a cluster of acidic amino acid residues and two divalent metal ions, forming a well organised ribonuclease active site. The distribution of the catalytic-site residues of the VapC-15 toxin is similar to that of T4 RNase H and of Methanococcus jannaschii FEN-1, providing strong evidence that these three proteins share a similar mechanism of activity. The presence of both VapB2C2 and VapBC2 emphasizes the fact that the same antitoxin can bind the toxin in 1:1 and 1:2 ratios. The crystal structure determination of the VapBC-15 complex reveals for the first time a PIN-domain ribonuclease protein that shows two metal ions at the active site and a variable mode of toxin-antitoxin assembly. The structure further shows that VapB-15 antitoxin binds to the same groove meant for the binding of putative substrate (RNA), resulting in the inhibition of VapC-15's toxicity.

KW - Antitoxins/metabolism

KW - Bacterial Proteins/metabolism

KW - Bacterial Toxins/metabolism

KW - DNA-Binding Proteins/metabolism

KW - Membrane Glycoproteins/metabolism

KW - Models, Molecular

KW - Mycobacterium tuberculosis/metabolism

KW - Protein Structure, Tertiary

KW - Ribonucleases/metabolism

KW - X-Ray Diffraction

U2 - 10.1016/j.jsb.2014.10.002

DO - 10.1016/j.jsb.2014.10.002

M3 - SCORING: Journal article

C2 - 25450593

VL - 188

SP - 249

EP - 258

JO - J STRUCT BIOL

JF - J STRUCT BIOL

SN - 1047-8477

IS - 3

ER -