| Structural highlights
Function
LPPM_MYCTU A putative lipoprotein that seems to be specialized for the initial steps of macrophage infection (PubMed:27220037). A non-acylated fragment (residues 26-185) binds phosphatidyl-myo-inositol mannosides (PIMs) (PubMed:27568926). Limits, in a TLR2-dependent fashion, bacterial uptake by host (mouse); this effect may be mediated by nonacylated fragment 26-185 (PubMed:27220037). Plays a TLR2-dependent role in host phagosome maturation arrest (PubMed:20844580, PubMed:27220037). Plays a TLR2-independent role in chemokine production during the first 24 hours of mouse infection (PubMed:27220037).[1] [2] [3]
Publication Abstract from PubMed
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.
Mycobacterium tuberculosis LppM Displays an Original Structure and Domain Composition Linked to a Dual Localization.,Barthe P, Veyron-Churlet R, de Visch A, Gilleron M, Saliou JM, Tomavo S, Nigou J, Brodin P, Cohen-Gonsaud M Structure. 2016 Aug 23. pii: S0969-2126(16)30220-9. doi:, 10.1016/j.str.2016.07.009. PMID:27568926[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Barthe P, Veyron-Churlet R, de Visch A, Gilleron M, Saliou JM, Tomavo S, Nigou J, Brodin P, Cohen-Gonsaud M. Mycobacterium tuberculosis LppM Displays an Original Structure and Domain Composition Linked to a Dual Localization. Structure. 2016 Aug 23. pii: S0969-2126(16)30220-9. doi:, 10.1016/j.str.2016.07.009. PMID:27568926 doi:http://dx.doi.org/10.1016/j.str.2016.07.009
- ↑ Brodin P, Poquet Y, Levillain F, Peguillet I, Larrouy-Maumus G, Gilleron M, Ewann F, Christophe T, Fenistein D, Jang J, Jang MS, Park SJ, Rauzier J, Carralot JP, Shrimpton R, Genovesio A, Gonzalo-Asensio JA, Puzo G, Martin C, Brosch R, Stewart GR, Gicquel B, Neyrolles O. High content phenotypic cell-based visual screen identifies Mycobacterium tuberculosis acyltrehalose-containing glycolipids involved in phagosome remodeling. PLoS Pathog. 2010 Sep 9;6(9):e1001100. PMID:20844580 doi:10.1371/journal.ppat.1001100
- ↑ Deboosère N, Iantomasi R, Queval CJ, Song OR, Deloison G, Jouny S, Debrie AS, Chamaillard M, Nigou J, Cohen-Gonsaud M, Locht C, Brodin P, Veyron-Churlet R. LppM impact on the colonization of macrophages by Mycobacterium tuberculosis. Cell Microbiol. 2017 Jan;19(1):e12619. PMID:27220037 doi:10.1111/cmi.12619
- ↑ Barthe P, Veyron-Churlet R, de Visch A, Gilleron M, Saliou JM, Tomavo S, Nigou J, Brodin P, Cohen-Gonsaud M. Mycobacterium tuberculosis LppM Displays an Original Structure and Domain Composition Linked to a Dual Localization. Structure. 2016 Aug 23. pii: S0969-2126(16)30220-9. doi:, 10.1016/j.str.2016.07.009. PMID:27568926 doi:http://dx.doi.org/10.1016/j.str.2016.07.009
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