title: Mycobacterium tuberculosis LppM Displays an Original Structure and Domain Composition Linked to a Dual Localization.
abstract: Mycobacterium tuberculosis (Mtb) encodes several bacterial effectors impacting the colonization of phagocytes. LppM (Rv2171) is both implicated in phagocytosis and able to efficiently block phagosomal acidification in the macrophage, two key processes contributing to Mtb persistence. We show that LppM is anchored to the mycobacterial cell wall by a C-terminal membrane domain. However, the protein also exists as a truncated protein secreted into the culture medium. The LppM solution structure we solve here displays no similarity with other Mtb lipoproteins also involved in phagosomal maturation (i.e., LprG). In addition, we demonstrate that the protein may be able to bind rare molecular species of phosphatidylinositol mannosides, bacterial compounds known to affect the host immune response. Thus, our data demonstrate a dual localization of LppM and provide a unique perspective on the regulation of protein secretion and localization in Mtb.
authors: Centre de Biochimie Structurale, CNRS UMR 5048, Inserm U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France.
authors: Philippe
authors: P
authors: Barthe
authors: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, France.
authors: Romain
authors: R
authors: Veyron-Churlet
authors: Centre de Biochimie Structurale, CNRS UMR 5048, Inserm U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France.
authors: Angélique
authors: A
authors: de Visch
authors: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, 31400 Toulouse, France.
authors: Martine
authors: M
authors: Gilleron
authors: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, France.
authors: Jean-Michel
authors: JM
authors: Saliou
authors: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, France.
authors: Stanislas
authors: S
authors: Tomavo
authors: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, 31400 Toulouse, France.
authors: Jérôme
authors: J
authors: Nigou
authors: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, France.
authors: Priscille
authors: P
authors: Brodin
authors: Centre de Biochimie Structurale, CNRS UMR 5048, Inserm U1054, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France. Electronic address: martin@cbs.cnrs.fr.
authors: Martin
authors: M
authors: Cohen-Gonsaud
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002473:Cell Wall / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D015964:Gene Expression Regulation, Bacterial; D008074:Lipoproteins / Q000737:chemistry* / Q000378:metabolism*; D013058:Mass Spectrometry; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000378:metabolism*; D010587:Phagocytosis; D010716:Phosphatidylinositols / Q000378:metabolism*; D000072417:Protein Domains; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D008074:Lipoproteins; D010716:Phosphatidylinositols; D020033:Protein Isoforms; C034154:phosphatidylinositol mannoside