In vitro dimerization of human RIO2 kinase

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 <i>in vitro</i>. 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 <i>in vitro</i> 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 <i>in vivo</i> and might function in maintaining the protein in an inactive state and could be employed during import.