TY  - INPR
A1  - Manger, Sina
A1  - Arghittu, Serena M.
A1  - Sprankel, Lasse
A1  - Meier-Credo, Jakob
A1  - Wieland, Konstantin
A1  - Schwalm, Martin P.
A1  - Bublak, Daniela
A1  - Knapp, Stefan
A1  - Langer, Julian David
A1  - Covino, Roberto
A1  - Frangakis, Achilleas S.
T1  - P116 from Mycoplasma is a self-sufficient lipid uptake and delivery machinery
T2  - bioRxiv
N2  - 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.
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/79460
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-794605
UR  - https://www.biorxiv.org/content/10.1101/2023.10.24.563710v1
IS  - 2023.10.24.563710 Version 1
PB  - bioRxiv
ER  -