A novel multi-domain C1qDC protein from Zhikong scallop Chlamys farreri provides new insights into the function of invertebrate C1qDC proteins

Dev Comp Immunol. 2015 Oct;52(2):202-14. doi: 10.1016/j.dci.2015.05.009. Epub 2015 Jun 3.

Abstract

The C1q domain containing (C1qDC) proteins are a family of proteins possessing globular C1q (gC1q) domains, and they rely on this domain to recognize various ligands such as PAMPs, immunoglobulins, ligands on apoptotic cell. In the present study, a novel multi-domain C1qDC protein (CfC1qDC-2) was identified from scallop Chlamys farreri, and its full length cDNA was composed of 1648 bp, encoding a signal peptide and three typical gC1q domains. BLAST analysis revealed significant sequence similarity between CfC1qDC-2 and C1qDC proteins from mollusks. Three gC1q domains were predicted in its tertiary structure to form a tightly packed bell-shaped trimer, and each one adopted a typical 10-stranded sandwich fold with a jelly-roll topology and contained six aromatic amino acids forming the hydrophobic core. The mRNA transcripts of CfC1qDC-2 were mainly detected in the tissues of hepatopancreas and gonad of adult scallops, and the expression level was up-regulated in hemocytes after stimulated by LPS, PGN and β-glucan. During the embryonic development of scallop, the mRNA transcripts of CfC1qDC-2 were presented in all the detected stages, and the expression level was up-regulated from D-hinged larvae and reached the highest at eye-spot larvae. The recombinant protein of MBP-CfC1qDC-2 (rCfC1qDC-2) could bind various PAMPs including LPS, PGN, LTA, β-glucan, mannan as well as polyI:C, and different microorganisms including three Gram-negative bacteria, three Gram-positive bacteria and two yeasts, as well as scallop apoptotic cells. Meanwhile, rCfC1qDC-2 could interact with human heat-aggregated IgG and IgM, and inhibit the C1q-dependent hemolysis of rabbit serum. All these results indicated that CfC1qDC-2 could recognize not only PAMPs as a PRR, but also the apoptotic cells. Moreover, the similar structures and functions shared by CfC1qDC-2 and complement C1q provided a new insight into the evolution of C1qDC proteins in complement system.

Keywords: Apoptotic cell binding; C1qDC proteins; Immune recognition; Immunoglobulin binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Base Sequence
  • Complement C1q / chemistry
  • Complement C1q / physiology*
  • Conserved Sequence
  • Gene Expression
  • Hemocytes / immunology
  • Hemocytes / metabolism
  • Hemolysis
  • Humans
  • Immunity, Innate
  • Immunoglobulin G / chemistry
  • Immunoglobulin M / chemistry
  • Lipopolysaccharides / pharmacology
  • Models, Molecular
  • Molecular Sequence Data
  • Organ Specificity
  • Pathogen-Associated Molecular Pattern Molecules / metabolism
  • Pectinidae / immunology*
  • Pectinidae / metabolism
  • Pectinidae / microbiology
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rabbits
  • Vibrio / immunology

Substances

  • Immunoglobulin G
  • Immunoglobulin M
  • Lipopolysaccharides
  • Pathogen-Associated Molecular Pattern Molecules
  • Complement C1q