4CHG

Crystal structure of VapBC15 complex from Mycobacterium tuberculosis

Summary for 4CHG

• Entry DOI: 10.2210/pdb4chg/pdb
• Descriptor: PROBABLE RIBONUCLEASE VAPC15, ANTITOXIN VAPB15, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: toxin-antitoxin complex, pin domain, toxin/antitoxin
• Biological source: MYCOBACTERIUM TUBERCULOSIS; More
• Total number of polymer chains: 10
• Total formula weight: 130240.79

Authors

Das, U.,Pogenberg, V.,Tiruttani Subhramanyam, U.K.,Wilmanns, M.,Srinivasan, A.,Gourinath, S. (deposition date: 2013-12-02, release date: 2014-11-12, Last modification date: 2024-10-23)

Primary citation

Das, U.,Pogenberg, V.,Subhramanyam, U.K.T.,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., 188:249-, 2014

PubMed 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 2.1Å 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.

PubMed: 25450593
DOI: 10.1016/J.JSB.2014.10.002

Experimental method

X-RAY DIFFRACTION (2.1 Å)