A Novel C1q Domain-Containing Protein Isolated from the Mollusk Modiolus kurilensis Recognizing Glycans Enriched with Acidic Galactans and Mannans

Abstract

C1q domain-containing (C1qDC) proteins are a group of biopolymers involved in immune response as pattern recognition receptors (PRRs) in a lectin-like manner. A new protein MkC1qDC from the hemolymph plasma of Modiolus kurilensis bivalve mollusk widespread in the Northwest Pacific was purified. The isolation procedure included ammonium sulfate precipitation followed by affinity chromatography on pectin-Sepharose. The full-length MkC1qDC sequence was assembled using de novo mass-spectrometry peptide sequencing complemented with N-terminal Edman’s degradation, and included 176 amino acid residues with molecular mass of 19 kDa displaying high homology to bivalve C1qDC proteins. MkC1qDC demonstrated antibacterial properties against Gram-negative and Gram-positive strains. MkC1qDC binds to a number of saccharides in Ca2+-dependent manner which characterized by structural meta-similarity in acidic group enrichment of galactose and mannose derivatives incorporated in diversified molecular species of glycans. Alginate, κ-carrageenan, fucoidan, and pectin were found to be highly effective inhibitors of MkC1qDC activity. Yeast mannan, lipopolysaccharide (LPS), peptidoglycan (PGN) and mucin showed an inhibitory effect at concentrations three orders of magnitude greater than for the most effective saccharides. MkC1qDC localized to the mussel hemal system and interstitial compartment. Intriguingly, MkC1qDC was found to suppress proliferation of human adenocarcinoma HeLa cells in a dose-dependent manner, indicating to the biomedical potential of MkC1qDC protein.

Invertebrate C1q Domain-Containing Proteins: Molecular Structure, Functional Properties and Biomedical Potential

“…The protein was detected in association with connective tissue fibers in mantle edge and digestive glands, in kidney concretions, as well as in interstitial space and the hemal system of all organs. Thus, the most intensively labeled organs were gills and pericardium with largest hemal sinuses and vessels [61]. The reason for such a distribution can be the same as in the SghC1qDC case because MkC1qDC is also a soluble protein.…”

“…Most of the studied C1qDC proteins have been obtained in recombinant form. Only a few C1qDC proteins have been isolated and described in their native forms, such as SghC1qDC (OXYL) from the feather lily Anneissia japonica [25] and MkC1qDC recently isolated by us from the mussel Modiolus kurilensis [61]. The linear domain structure of C1qDC proteins was determined using SMART [62] (Figure 2).…”

“…The fact of binding to pathogens and their components is not fully indicative of the functional role of the protein. Therefore, the ability to agglutinate microorganisms [25,47,51,53,61,[93][94][95], inhibit their growth [25,41,55,61], and enhance phagocytosis and chemotaxis [46,[48][49][50]56,88,93,95] is often additionally assessed. SghC1qDC from A. japonica was tested only with P. aeruginosa, whose agglutination is inhibited by the co-presence of N-acetyllactosamine, but not lactose or LPS.…”

Identification of Putative Molecules for Adiponectin and Adiponectin Receptor and Their Roles in Learning and Memory in Lymnaea stagnalis

“…The function between the C1q protein and adiponectin is different in mammals: they complement system and glucose-level regulation, respectively. In molluscs, several C1q-related and C1q-domain-containing proteins were isolated, and these proteins are suggested to be involved in molluscan immune systems [ 24 , 25 , 26 ]. However, in mammals, adiponectin can bind with the C1q complex and activate the classical complement pathway [ 27 ].…”

Coming New Age of Marine Glycomics: The Fundamental, Medical, and Ecological Aspects

“…Grinchenko, Kriegsheim, Shved et al, have reported the biochemical properties of the novel C1q domain containing protein, MkC1qDC, from the hemolymph of the bivalve mollusk Modiolus kurilensis [ 10 ]. MkC1qDC showed a lectin-like activity by binding galactose and mannose with a requirement of Ca2+.…”