Structure and activity of a novel archaeal β-CASP protein with N-terminal KH domains

Ana P G Silva, Maria Chechik, Robert T. Byrne, David G. Waterman, Chyan Leong Ng, Eleanor J. Dodson, Eugene V. Koonin, Alfred A. Antson, Callum Smits

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

MTH1203, a β-CASP metallo-β-lactamase family nuclease from the archaeon Methanothermobacter thermautotrophicus, was identified as a putative nuclease that might contribute to RNA processing. The crystal structure of MTH1203 reveals that, in addition to the metallo-β-lactamase nuclease and the β-CASP domains, it contains two contiguous KH domains that are unique to MTH1203 and its orthologs. RNA-binding experiments indicate that MTH1203 preferentially binds U-rich sequences with a dissociation constant in the micromolar range. In vitro nuclease activity assays demonstrated that MTH1203 is a zinc-dependent nuclease. MTH1203 is also shown to be a dimer and, significantly, this dimerization enhances the nuclease activity. Transcription termination in archaea produces mRNA transcripts with U-rich 3′ ends that could be degraded by MTH1203 considering its RNA-binding specificity. We hypothesize that this nuclease degrades mRNAs of proteins targeted for degradation and so regulates archaeal RNA turnover, possibly in concert with the exosome.

Original languageEnglish
Pages (from-to)622-632
Number of pages11
JournalStructure
Volume19
Issue number5
DOIs
Publication statusPublished - 11 May 2011
Externally publishedYes

Fingerprint

Archaeal Proteins
Archaea
RNA
Archaeal RNA
Methanobacteriaceae
Exosomes
Messenger RNA
Dimerization
Proteolysis
Zinc

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Silva, A. P. G., Chechik, M., Byrne, R. T., Waterman, D. G., Ng, C. L., Dodson, E. J., ... Smits, C. (2011). Structure and activity of a novel archaeal β-CASP protein with N-terminal KH domains. Structure, 19(5), 622-632. https://doi.org/10.1016/j.str.2011.03.002

Structure and activity of a novel archaeal β-CASP protein with N-terminal KH domains. / Silva, Ana P G; Chechik, Maria; Byrne, Robert T.; Waterman, David G.; Ng, Chyan Leong; Dodson, Eleanor J.; Koonin, Eugene V.; Antson, Alfred A.; Smits, Callum.

In: Structure, Vol. 19, No. 5, 11.05.2011, p. 622-632.

Research output: Contribution to journalArticle

Silva, APG, Chechik, M, Byrne, RT, Waterman, DG, Ng, CL, Dodson, EJ, Koonin, EV, Antson, AA & Smits, C 2011, 'Structure and activity of a novel archaeal β-CASP protein with N-terminal KH domains', Structure, vol. 19, no. 5, pp. 622-632. https://doi.org/10.1016/j.str.2011.03.002
Silva, Ana P G ; Chechik, Maria ; Byrne, Robert T. ; Waterman, David G. ; Ng, Chyan Leong ; Dodson, Eleanor J. ; Koonin, Eugene V. ; Antson, Alfred A. ; Smits, Callum. / Structure and activity of a novel archaeal β-CASP protein with N-terminal KH domains. In: Structure. 2011 ; Vol. 19, No. 5. pp. 622-632.
@article{b89c700de12b4c198a522c794ea4869c,
title = "Structure and activity of a novel archaeal β-CASP protein with N-terminal KH domains",
abstract = "MTH1203, a β-CASP metallo-β-lactamase family nuclease from the archaeon Methanothermobacter thermautotrophicus, was identified as a putative nuclease that might contribute to RNA processing. The crystal structure of MTH1203 reveals that, in addition to the metallo-β-lactamase nuclease and the β-CASP domains, it contains two contiguous KH domains that are unique to MTH1203 and its orthologs. RNA-binding experiments indicate that MTH1203 preferentially binds U-rich sequences with a dissociation constant in the micromolar range. In vitro nuclease activity assays demonstrated that MTH1203 is a zinc-dependent nuclease. MTH1203 is also shown to be a dimer and, significantly, this dimerization enhances the nuclease activity. Transcription termination in archaea produces mRNA transcripts with U-rich 3′ ends that could be degraded by MTH1203 considering its RNA-binding specificity. We hypothesize that this nuclease degrades mRNAs of proteins targeted for degradation and so regulates archaeal RNA turnover, possibly in concert with the exosome.",
author = "Silva, {Ana P G} and Maria Chechik and Byrne, {Robert T.} and Waterman, {David G.} and Ng, {Chyan Leong} and Dodson, {Eleanor J.} and Koonin, {Eugene V.} and Antson, {Alfred A.} and Callum Smits",
year = "2011",
month = "5",
day = "11",
doi = "10.1016/j.str.2011.03.002",
language = "English",
volume = "19",
pages = "622--632",
journal = "Structure with Folding & design",
issn = "0969-2126",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Structure and activity of a novel archaeal β-CASP protein with N-terminal KH domains

AU - Silva, Ana P G

AU - Chechik, Maria

AU - Byrne, Robert T.

AU - Waterman, David G.

AU - Ng, Chyan Leong

AU - Dodson, Eleanor J.

AU - Koonin, Eugene V.

AU - Antson, Alfred A.

AU - Smits, Callum

PY - 2011/5/11

Y1 - 2011/5/11

N2 - MTH1203, a β-CASP metallo-β-lactamase family nuclease from the archaeon Methanothermobacter thermautotrophicus, was identified as a putative nuclease that might contribute to RNA processing. The crystal structure of MTH1203 reveals that, in addition to the metallo-β-lactamase nuclease and the β-CASP domains, it contains two contiguous KH domains that are unique to MTH1203 and its orthologs. RNA-binding experiments indicate that MTH1203 preferentially binds U-rich sequences with a dissociation constant in the micromolar range. In vitro nuclease activity assays demonstrated that MTH1203 is a zinc-dependent nuclease. MTH1203 is also shown to be a dimer and, significantly, this dimerization enhances the nuclease activity. Transcription termination in archaea produces mRNA transcripts with U-rich 3′ ends that could be degraded by MTH1203 considering its RNA-binding specificity. We hypothesize that this nuclease degrades mRNAs of proteins targeted for degradation and so regulates archaeal RNA turnover, possibly in concert with the exosome.

AB - MTH1203, a β-CASP metallo-β-lactamase family nuclease from the archaeon Methanothermobacter thermautotrophicus, was identified as a putative nuclease that might contribute to RNA processing. The crystal structure of MTH1203 reveals that, in addition to the metallo-β-lactamase nuclease and the β-CASP domains, it contains two contiguous KH domains that are unique to MTH1203 and its orthologs. RNA-binding experiments indicate that MTH1203 preferentially binds U-rich sequences with a dissociation constant in the micromolar range. In vitro nuclease activity assays demonstrated that MTH1203 is a zinc-dependent nuclease. MTH1203 is also shown to be a dimer and, significantly, this dimerization enhances the nuclease activity. Transcription termination in archaea produces mRNA transcripts with U-rich 3′ ends that could be degraded by MTH1203 considering its RNA-binding specificity. We hypothesize that this nuclease degrades mRNAs of proteins targeted for degradation and so regulates archaeal RNA turnover, possibly in concert with the exosome.

UR - http://www.scopus.com/inward/record.url?scp=79955860702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955860702&partnerID=8YFLogxK

U2 - 10.1016/j.str.2011.03.002

DO - 10.1016/j.str.2011.03.002

M3 - Article

C2 - 21565697

AN - SCOPUS:79955860702

VL - 19

SP - 622

EP - 632

JO - Structure with Folding & design

JF - Structure with Folding & design

SN - 0969-2126

IS - 5

ER -