Crystal structure of the putative cell-wall lipoglycan biosynthesis protein LmcA from Mycobacterium smegmatis.
Acta Crystallogr D Struct Biol
; 78(Pt 4): 494-508, 2022 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-35362472
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 1.8â
Å resolution. The structure revealed an elongated ß-barrel fold enclosing two distinct cavities and one α-helix extending away from the ß-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 ß-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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Corynebacterium glutamicum
/
Mycobacterium tuberculosis
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Acta Crystallogr D Struct Biol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Austrália