An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

Abstract

The crystal and solution structures of the T. thermophilus NlpC/P60 d,l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan.

The Structural Basis of Ligand Perception and Signal Activation by Receptor Kinases

“…Consistently, chitin octamers but not shorter fragments promote ligand-induced homodimerization of the AtCERK1 ectodomains in vitro (77). LysM-domain oligomerization on longer NAG-containing carbohydrate oligomers has been visualized in crystal structures of bacterial and fungal LysM-containing proteins (29,134), but an active LysM-RK signaling complex remains to be characterized.…”

“…It also remains to be determined what types of carbohydrates are sensed by OsCERK1, which does not detectably bind chitin oligomers in vitro (76). All plant LysM domains show a high degree of structural conservation with bacterial LysM proteins, such as the bacterial endopeptidase NlpC/P60 (134) (Figure 3e). It can thus be assumed that the extracellular ligand-binding domains of plant LysM receptors have evolved from ancestral LysM proteins, as has been suggested for the ectodomains of plant cytokinin receptors (50).…”

LysMD3 is a type II membrane protein without an role in the response to a range of pathogens

“…LysMD3 is named for its N-terminal lysin motif (LysM) and, in mice and humans, is a member of a protein family that also includes LysMD1, LysMD2, and LysMD4. Recent studies of bacterial and plant LysMs suggest that LysMs bind the glycan backbone of peptidoglycan, or the related molecule chitin (2)(3)(4)(5)(6). While peptidoglycan is a ubiquitous bacterial component, relatively little is known about its interactions with the mammalian immune system.…”

Lipo-chitooligosaccharidic nodulation factors and their perception by plant receptors

“…The ligand-binding site was located in the central LysM (LysM2) and the model proposes that a chitin octamer, which is a symmetric ligand, accommodates this binding site by inducing homodimerization of AtCERK1 that would lead to receptor activation. An alternative mode of chitin binding involving an intermolecular mechanism with multiple LysM domains has also been reported from structural studies on the bacterial Thermus thermophilus NlpC/P60 endopeptidase [59]. Other LysM proteins in A. thaliana, AtLYK4 and AtLYK5 acting in complex with AtCERK1, have been reported to bind chitin and are important for innate immunity [60,61].…”