title: Structural basis and function of XRN2 binding by XTB domains.
abstract: The RNase XRN2 is essential in RNA metabolism. In Caenorhabditis elegans, XRN2 functions with PAXT-1, which shares a putative XRN2-binding domain (XTBD) with otherwise unrelated mammalian proteins. Here, we characterize the structure and function of an XTBD-XRN2 complex. Although XTBD stably interconnects two XRN2 domains through numerous interacting residues, mutation of a single critical residue suffices to disrupt XTBD-XRN2 complexes in vitro and to recapitulate paxt-1-null mutant phenotypes in vivo. Demonstrating conservation of function, vertebrate XTBD-containing proteins bind XRN2 in vitro, and human CDKN2AIPNL (HsC2AIL) can substitute for PAXT-1 in vivo. In vertebrates, which express three distinct XTBD-containing proteins, XRN2 may partition into distinct stable heterodimeric complexes, which probably differ in subcellular localization or function. In C. elegans, complex formation with PAXT-1, the sole XTBD protein, serves to preserve the stability of XRN2 in the absence of substrate.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Richter
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Iskra
authors.initials: I
authors.lastname: Katic
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Heinz
authors.initials: H
authors.lastname: Gut
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Helge
authors.identifier: http://orcid.org/0000-0002-8169-6905
authors.initials: H
authors.lastname: Großhans
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005095:Exoribonucleases / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C000608560:PAXT-1 protein, C elegans; D005095:Exoribonucleases; C544213:XRN-2 protein, C elegans