P116 from Mycoplasma is a self-sufficient lipid uptake and delivery machinery

  • Lipid acquisition and transport are fundamental processes in all organisms, but many of the key players remain unidentified. Here, we elucidate the lipid-cycling mechanism of the Mycoplasma pneumoniae membrane protein P116. We show that P116 not only extracts lipids from its environment but also self-sufficiently deposits them into both bacterial and eukaryotic cell membranes as well as liposomes. Our structures and molecular dynamics simulation show that the N-terminal region of P116, which resembles an SMP domain, is responsible for perturbing the membrane, while a hydrophobic pocket exploits the chemical gradient to collect the lipids and the protein’s dorsal side acts as a mediator of membrane directionality. Furthermore, ligand binding and growth curve assays suggest the potential for designing small molecule inhibitors targeting this essential and immunodominant protein. We show that P116 is a versatile lipid acquisition and delivery machinery that shortcuts the multi-protein pathways used by more complex organisms. Thus, our work advances the understanding of common lipid transport strategies, which may aid research into the mechanisms of more complex lipid-handling machineries.

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Author:Sina MangerORCiD, Serena M. ArghittuORCiD, Lasse SprankelORCiDGND, Jakob Meier-CredoORCiD, Konstantin Wieland, Martin P. SchwalmORCiD, Daniela Bublak, Stefan KnappORCiDGND, Julian David LangerORCiDGND, Roberto CovinoORCiD, Achilleas S. FrangakisORCiDGND
URN:urn:nbn:de:hebis:30:3-794605
URL:https://www.biorxiv.org/content/10.1101/2023.10.24.563710v1
DOI:https://doi.org/10.1101/2023.10.24.563710
Parent Title (English):bioRxiv
Publisher:bioRxiv
Document Type:Preprint
Language:English
Date of Publication (online):2023/10/24
Date of first Publication:2023/10/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/03/07
Issue:2023.10.24.563710 Version 1
Edition:Version 1
Page Number:46
HeBIS-PPN:516889133
Institutes:Angeschlossene und kooperierende Institutionen / MPI für Biophysik
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY-NC - Namensnennung - Nicht kommerziell 4.0 International