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Structural characterization of an essential lipoprotein of Mycoplasma pneumoniae

Keles, I.; Manger, S.; Mantanya, M. S.; Frangakis, A. S.

2024-09-06 biophysics
10.1101/2024.09.05.611430 bioRxiv
Show abstract

Mycoplasma pneumoniae is a human pathogen causing atypical community-acquired pneumonia. It serves as a model for a minimal cell and is notable for its absent cell wall, minimal genome, and use of antigenic variation to evade the host immune response. Here, we report the structures of the essential surface proteins Mpn444 and Mpn436 at 3.74 Angstrom and 3.65 Angstrom resolution, and the molecular architecture of the Mpn444 homotrimeric complex. We show that both proteins include a peptidyl-prolyl isomerase (PPIase) domain and a chaperone-like domain. In vitro PPIase activity assays suggest that Mpn444 and Mpn436 function as extracellular foldases in Mycoplasma species. Furthermore, both proteins are conserved across multiple Mycoplasma species. We built a composite model integrating previously reported interactions from crosslinking and cryo-ET data and we conclude that Mpn444 is responsible for the extracellular folding of nascent protein chains. Our work underscores the potential of Mpn444 and Mpn436 as a target for the development of novel strategies to treat mycoplasma infections.

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