MoxR AAA+ ATPases: a novel family of molecular chaperones?

Abstract

The MoxR AAA+ family is a large, diverse group of ATPases that, so far, has been poorly studied. Members of this family are found throughout the Bacteria and Archaea superkingdoms, but have not yet been detected in Eukaryota. The limited experimental data available to date suggest that members of this family might have chaperone-like activities. Here we present an extensive phylogenetic analysis which builds upon our previously published work, and reveals that the MoxR family can be divided into at least seven subfamilies, including MoxR Proper (MRP), TM0930, RavA, CGN, APE2220, PA2707, and YehL. We also include a comprehensive overview and gene context analysis for each of these subfamilies. Our data reveal distinct conserved associations of certain MoxR family members with specific genes, including further support for our previously reported observation that many members of the MoxR AAA+ family are found near Von Willebrand Factor Type A (VWA) proteins and are likely to function with them. We propose, based on bioinformatic analyses and the available literature, that the MoxR AAA+ proteins function with VWA domain-containing proteins to form a chaperone system that is important for the folding/activation of proteins and protein complexes by primarily mediating the insertion of metal cofactors into the substrate molecules.