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Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane

dc.rights.licenseopenen_US
dc.contributor.authorBROWN, Chelsea
dc.contributor.authorCOREY, Robin
hal.structure.identifierInstitut Européen de Chimie et Biologie [IECB]
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorGRELARD, Axelle
dc.contributor.authorGAO, Ya
dc.contributor.authorCHOI, Yeol Kyo
dc.contributor.authorLUNA, Emanuel
dc.contributor.authorGILLERON, Martine
dc.contributor.authorDESTAINVILLE, Nicolas
dc.contributor.authorNIGOU, Jerome
hal.structure.identifierInstitut Européen de Chimie et Biologie [IECB]
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLOQUET, Antoine
dc.contributor.authorFULLAM, Elizabeth
dc.contributor.authorIM, Wonpil
dc.contributor.authorSTANSFELD, Phillip
dc.contributor.authorCHAVENT, Matthieu
dc.date.accessioned2024-04-24T13:36:30Z
dc.date.available2024-04-24T13:36:30Z
dc.date.issued2023-01-31
dc.identifier.issn0027-8424en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/199320
dc.description.abstractEnMycobacterium tuberculosis ( Mtb ) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. The current treatment regime is long and expensive, and missed doses contribute to drug resistance. Therefore, development of new anti-TB drugs remains one of the highest public health priorities. Mtb has evolved a complex cell envelope that represents a formidable barrier to antibiotics. The Mtb cell envelop consists of four distinct layers enriched for Mtb specific lipids and glycans. Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. However, the role of PIMs in the structure and function of the membrane remains elusive. Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. To further validate the model, we tested known anti-TB drugs and demonstrated that our models agree with experimental results. Thus, our work sheds new light on the organization of the mycobacterial plasma membrane. This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function.
dc.language.isoENen_US
dc.subject.enantibiotics diffusion
dc.subject.enmulti-scale molecular dynamics
dc.subject.enmycobacteria inner membrane
dc.subject.enphosphatidyl-myoinositol mannosides
dc.title.enSupramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane
dc.typeArticle de revueen_US
dc.identifier.doi10.1073/pnas.2212755120en_US
dc.subject.halPhysique [physics]/Physique [physics]/Biophysique [physics.bio-ph]en_US
bordeaux.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
bordeaux.pagee2212755120en_US
bordeaux.volume120en_US
bordeaux.hal.laboratoriesCBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-04037054
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20of%20the%20United%20States%20of%20America&rft.date=2023-01-31&rft.volume=120&rft.issue=5&rft.spage=e2212755120&rft.epage=e2212755120&rft.eissn=0027-8424&rft.issn=0027-8424&rft.au=BROWN,%20Chelsea&COREY,%20Robin&GRELARD,%20Axelle&GAO,%20Ya&CHOI,%20Yeol%20Kyo&rft.genre=article


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