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

Structure (London, England : 1993)

PubMedID: 21565697

Silva AP, Chechik M, Byrne RT, Waterman DG, Ng CL, Dodson EJ, Koonin EV, Antson AA, Smits C. Structure and activity of a novel archaeal ß-CASP protein with N-terminal KH domains. Structure. 2011;19(5):622-32.
MTH1203, a ß-CASP metallo-ß-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-ß-lactamase nuclease and the ß-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.