In vitro dimerization of human RIO2 kinase

RNA Biol. 2019 Nov;16(11):1633-1642. doi: 10.1080/15476286.2019.1653679. Epub 2019 Aug 14.

Abstract

RIO proteins form a conserved family of atypical protein kinases. RIO2 is a serine/threonine protein kinase/ATPase involved in pre-40S ribosomal maturation. Current crystal structures of archaeal and fungal Rio2 proteins report a monomeric form of the protein. Here, we describe three atomic structures of the human RIO2 kinase showing that it forms a homodimer in vitro. Upon self-association, each protomer ATP-binding pocket is partially remodelled and found in an apostate. The homodimerization is mediated by key residues previously shown to be responsible for ATP binding and catalysis. This unusual in vitro protein kinase dimer reveals an intricate mechanism where identical residues are involved in substrate binding and oligomeric state formation. We speculate that such an oligomeric state might be formed also in vivo and might function in maintaining the protein in an inactive state and could be employed during import.

Keywords: 40S; RIO2; Ribosome biogenesis; atypical kinase; dimer; protomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Crystallography, X-Ray
  • Humans
  • In Vitro Techniques
  • Models, Molecular
  • Protein Conformation
  • Protein Multimerization
  • Protein Serine-Threonine Kinases / chemistry*
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Structure, Secondary

Substances

  • Adenosine Triphosphate
  • Protein Serine-Threonine Kinases
  • RIOK2 protein, human

Grant support

This work was supported by an ANR Blanc 2010 grant RIBOPRE40S, University of Bordeaux, CNRS and INSERM. The authors acknowledge the support and the use of resources of the French Infrastructure for Integrated Structural Biology FRISBI ANR-10-INBS-05 and of Instruct-ERIC;Agence Nationale de la Recherche [ANR-10-INBS-05];Agence Nationale de la Recherche [RIBOPRE40S].