Journal Article

PUBDB-2015-01365

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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 Assemblypetea

Das, U. (Corresponding Author)>Extern* ; Pogenberg, V.>Extern*EMBL* ; Subhramanyam, U. K. T. ; Wilmanns, M.>Extern*EMBL* ; Gourinath, S. ; Srinivasan, A.

2014
Elsevier San Diego, Calif.

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Please use a persistent id in citations: doi:10.1016/j.jsb.2014.10.002

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 Å resolution. The VapB-15 and VapC-15 components assemble into one heterotetramer (VapB$_2$C$_2$) and two heterotrimers (VapBC$_2$) 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 VapB$_2$C$_2$ and VapBC$_2$ 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.

Note: (c) Elsevier Inc. Post referee full text in progress. Embargo for full text 1 year from 22. Oct. 2014.

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Contributing Institute(s):

1. EMBL (EMBL)

Research Program(s):

1. PETRA Beamline P13 (POF2-54G14) (POF2-54G14)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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