Structural basis and function of XRN2 binding by XTB domains

Nature Structural & Molecular Biology
Hannes RichterHelge Großhans

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.

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Citations

Feb 6, 2020·The Biochemical Journal·Jana AlexandrovaAnne E Willis
Jun 17, 2020·Proteins·Archana S BhatNick V Grishin
May 13, 2021·Nucleic Acids Research·Zuzer DhoondiaAthar Ansari
Oct 13, 2017·Chemical Reviews·Cedric BelairSandra L Wolin
Apr 17, 2019·Analytical Chemistry·Wenjuan ZengFuyi Wang
Sep 7, 2021·Cell Structure and Function·Ilkin Aygün, Takashi S Miki

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Methods Mentioned

BETA
dissection
light scattering
Immobilized
co-immunoprecipitation
transgenic
PCR
Assay
FCS
transfection
Protein Assay

Software Mentioned

HHPred
XDS
COOT
DisEMBL
ConSurf
PSIPRED Protein Analysis Workbench
MosSCI
PSIPRED
DALI
PyMOL

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