Molecular basis for bacterial peptidoglycan recognition by LysM domains

Abstract

Carbohydrate recognition is essential for growth, cell adhesion and signalling in all living organisms. A highly conserved carbohydrate binding module, LysM, is found in proteins from viruses, bacteria, fungi, plants and mammals. LysM modules recognize polysaccharides containing N-acetylglucosamine (GlcNAc) residues including peptidoglycan, an essential component of the bacterial cell wall. However, the molecular mechanism underpinning LysM–peptidoglycan interactions remains unclear. Here we describe the molecular basis for peptidoglycan recognition by a multimodular LysM domain from AtlA, an autolysin involved in cell division in the opportunistic bacterial pathogen Enterococcus faecalis. We explore the contribution of individual modules to the binding, identify the peptidoglycan motif recognized, determine the structures of free and bound modules and reveal the residues involved in binding. Our results suggest that peptide stems modulate LysM binding to peptidoglycan. Using these results, we reveal how the LysM module recognizes the GlcNAc-X-GlcNAc motif present in polysaccharides across kingdoms.

Hydrolysis of peptidoglycan is modulated by amidation of meso‐diaminopimelic acid and Mg2+ in Bacillus subtilis

“…For example, a common modification is the deacetylation of N‐acetyl glucosamine. This modification abolishes the binding of LysM domain containing proteins, such as some autolysins and PG hydrolases, and may thereby modulate their activity (Mesnage et al ., 2014). A distinct and widespread modification is the O‐acetylation of N‐acetyl muramic acid, which is associated to resistance to lysozyme and endogenous autolysis, as well as to resistance to penicillin and macrophage killing (Bernard et al ., 2011a; Davis and Weiser, 2011).…”

The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division

“…The cell wall amidases AmiB and AmiC of E. coli and the type IVa secretion apparatus of P. aeruginosa are targeted to division sites by peptidoglycan-binding AMIN domains (8,(61)(62)(63)(64). One of the most widespread PG-binding domains is the LysM domain, which binds to carbohydrates containing GlcNAc, including PG in bacteria and chitin in eukaryotes (65,66). LysM domains mediate septal localization of several PG hydrolases in Gram-positive bacteria (9,67,68).…”

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.…”