7N3V

Crystal structure of Mycobacterium smegmatis LmcA

Summary for 7N3V

• Entry DOI: 10.2210/pdb7n3v/pdb
• Descriptor: LmcA, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: lipoglycan biosynthesis, mannosyltransferase, mycobacterium, unknown function
• Biological source: Mycolicibacterium smegmatis (Mycobacterium smegmatis)
• Total number of polymer chains: 2
• Total formula weight: 69400.16

Authors

Patel, O.,Lucet, I.,Panjikar, S. (deposition date: 2021-06-02, release date: 2022-04-13, Last modification date: 2024-05-22)

Primary citation

Patel, O.,Brammananth, R.,Dai, W.,Panjikar, S.,Coppel, R.L.,Lucet, I.S.,Crellin, P.K.
Crystal structure of the putative cell-wall lipoglycan biosynthesis protein LmcA from Mycobacterium smegmatis.
Acta Crystallogr D Struct Biol, 78:494-508, 2022

PubMed Abstract: The bacterial genus Mycobacterium includes important pathogens, most notably M. tuberculosis, which infects one-quarter of the entire human population, resulting in around 1.4 million deaths from tuberculosis each year. Mycobacteria, and the closely related corynebacteria, synthesize a class of abundant glycolipids, the phosphatidyl-myo-inositol mannosides (PIMs). PIMs serve as membrane anchors for hyperglycosylated species, lipomannan (LM) and lipoarabinomannan (LAM), which are surface-exposed and modulate the host immune response. Previously, in studies using the model species Corynebacterium glutamicum, NCgl2760 was identified as a novel membrane protein that is required for the synthesis of full-length LM and LAM. Here, the first crystal structure of its ortholog in Mycobacterium smegmatis, MSMEG_0317, is reported at 1.8 Å resolution. The structure revealed an elongated β-barrel fold enclosing two distinct cavities and one α-helix extending away from the β-barrel core, resembling a `cone with a flake' arrangement. Through xenon derivatization and structural comparison with AlphaFold2-derived predictions of the M. tuberculosis homolog Rv0227c, structural elements were identified that may undergo conformational changes to switch from `closed' to `open' conformations, allowing cavity access. An AlphaFold2-derived NCgl2760 model predicted a smaller β-barrel core with an enclosed central cavity, suggesting that all three proteins, which were collectively termed LmcA, may have a common mechanism of ligand binding through these cavities. These findings provide new structural insights into the biosynthetic pathway for a family of surface lipoglycans with important roles in mycobacterial pathogenesis.

PubMed: 35362472
DOI: 10.1107/S2059798322001772

Experimental method

X-RAY DIFFRACTION (1.83 Å)