Crystal structure of the putative cell-wall lipoglycan biosynthesis protein LmcA from Mycobacterium smegmatis

Onisha Patel, Rajini Brammananth, Weiwen Dai, Santosh Panjikar, Ross L. Coppel, Isabelle S. Lucet, Paul K. Crellin

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)494-508
Number of pages15
JournalActa Crystallographica Section D: Structural Biology
Publication statusPublished - 1 Apr 2022


  • lipoarabinomannan
  • lipomannan
  • MSMEG-0317.
  • Mycobacterium smegmatis
  • Mycobacterium tuberculosis

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