Structural analysis of mycobacterium tuberculosis homologues of the eukaryotic proteasome assembly chaperone 2 (PAC2)

Abstract

A previous bioinformatics analysis identified the Mycobacterium tuberculosis proteins Rv2125 and Rv2714 as orthologs of the eukaryotic proteasome assembly chaperone 2 (PAC2). We set out to investigate whether Rv2125 or Rv2714 can function in proteasome assembly. We solved the crystal structure of Rv2125 at a resolution of 3.0 Å, which showed an overall fold similar to that of the PAC2 family proteins that include the archaeal PbaB and the yeast Pba1. However, Rv2125 and Rv2714 formed trimers, whereas PbaB forms tetramers and Pba1 dimerizes with Pba2. We also found that purified Rv2125 and Rv2714 could not bind to M. tuberculosis 20S core particles. Finally, proteomic analysis showed that the levels of known proteasome components and substrate proteins were not affected by disruption of Rv2125 in M. tuberculosis. Our work suggests that Rv2125 does not participate in bacterial proteasome assembly or function.