Lysozyme's lectin-like characteristics facilitates its immune defense function

Abstract

Abstract. Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.

Organism dual RNA‐seq reveals the importance of BarA/UvrY inVibrio parahaemolyticusvirulence

“…The encoding protein of these genes include (Figure 3B, Dataset S4): (i) C‐type lectins (such as CLEC‐10, CLEC‐40, and CLEC‐170), a family of surface receptors known to recognize microbial carbohydrate moieties, which can sense products from dying cells and transduce inflammatory signals that modulate the immune system 51 ; (ii) F‐box A protein (FBXA‐20, FBXA‐59, FBXA‐60, FBXA‐82, and FBXA‐156), one family proteins with F‐box motif that involves in ubiquitin‐mediated proteolysis, which function as the key regulator in many pathways of cell signalling, transcription, and cell division 52 ; (iii) Lysozymes. In C. elegans , there are ten genes encoding lysozymes for antimicrobial proteins against bacteria 53 . Our results showed that most of lysozymes in C. elegans were induced at different time point post infection, and LYS‐2 and LYS‐3 were consistently induced throughout the infection process (Figure 3B, Dataset S4).…”

Nanomedical Relevance of the Intermolecular Interaction Dynamics—Examples from Lysozymes and Insulins

“…The relation between pH values and lysozyme (HL and HEWL) structures is indicated by the overlay presentations shown in Figure 8c,d. When human lysozyme is encapsulated in nanoparticles for a therapeutic use, precise knowledge of the submolecular details about its carbohydrate affinity 14 is of importance because this part of the molecule can be considered as a vital target unit. Three essential amino acids—Tyr63 (yellow), Arg98 (red), and Trp109 (blue)—are stabilizing the complex (5lsh.pdb), highlighted in Figure 8e.…”

“…(d) Overlay of two human lysozyme (HL) structures for a comparison of pH-dependent effects. (e) Backbone and (f) surface representation of human lysozyme in complex with the tetrasaccharide O-antigen LPS fragment from K. pneumoniae (5lsh.pdb 14 ). Crucial amino acids that are stabilizing the complex are highlighted on the left side by the following color code: Tyr63 (yellow), Arg98 (red), and Trp109 (blue).…”

“…In the case of lysozymes, the results on specific interactions with the carbohydrate part of the LPS chains on pathogen surfaces have just been published. 14 The findings with respect to an intrinsic molecular target function can be combined with the concept of targeting peptides on the surfaces of nanoparticles. When protein drugs are delivered by nanoparticles with target-directed absorption enhancers (e.g., certain collagen fragments) on their surfaces, the molecular fine-tuning of all components of the delivery system is the crucial step for a therapeutic success.…”

Editorial: O-specific polysaccharide confers lysozyme resistance to extraintestinal pathogenic Escherichia coli

“…Some insights on molecular basics of LPS binding by LZ were recently provided by Zhang et al. who used precise methodology (NMR spectroscopy, molecular modeling, and X-ray crystallography) to study interactions between human LZ and synthetic oligosaccharides representing repeating unit(s) of K. pneumoniae O1 O-PS [ 26 ]. The LZ molecules underwent structural rearrangements after the interaction with synthetic oligosaccharides.…”