The Ancient Microbial RIO Kinases

Nicole A Laronde

doi:10.1074/jbc.r113.538090

Abstract

The RIO kinases existed before the split between Archaea and Eubacteria and are essential in eukaryotes. Although much has been elucidated in the past few years regarding the function of these proteins in eukaryotes, questions remain about their role in prokaryotes. Comparison of structure and sequence suggests that the ancient RIO kinases may have similar functional properties in prokaryotes as they do in eukaryotes. The conservation of charge distribution, functional residues, and overall structure supports a role for these proteins in ribosome interactions, as is their purpose in eukaryotes. However, a lack of study in this area has left little direct evidence in support of this function.

Highlights

The Ancient Microbial RIO Kinases*Rio and Rio are found in most archaea and all eukaryotes, Rio is found in multicellular eukaryotes, and RioB is found in some archaea and some eubacteria [3, 4]
The invariant catalytic residues present in the C-terminal lobe of ePKs, including asparagine and aspartic acid residues on the catalytic loop (C-loop) and an aspartic acid residue on the metal-binding loop (M-loop), are all conserved in the RIO kinase domains, suggesting that they catalyze phosphoryl transfer as well (Fig. 2)
RIO kinases have a distinct phosphate-binding loop (P-loop) that is subfamily-specific (Fig. 2A) and a flexible loop (F-loop) region that is located in the N-terminal lobe

Summary

The Ancient Microbial RIO Kinases*

Rio and Rio are found in most archaea and all eukaryotes, Rio is found in multicellular eukaryotes, and RioB is found in some archaea and some eubacteria [3, 4] The existence of these proteins in prokaryotes establishes that they are at least 1.5 billion years older that canonical eukaryotic protein kinases (ePKs).. In a study on the evolution of the protein kinases, Leonard et al [5] suggested that the RIO kinases could be the ancestors of the canonical ePKs. the role of the RIO kinases in prokaryotes is not known, in eukaryotes, it is clear that RIO kinases are essential and are required for the synthesis of new ribosomes (6 – 8).

Structures of the RIO Kinases of Archaea

The Search for RIO Kinase Substrates

Known Functions of the RIO Kinases

RIO Kinases in Microbes

Development of Inhibitors Using Microbial RIO Kinases

Conclusions