A novel scavenger receptor-cysteine-rich (SRCR) domain containing scavenger receptor identified from mollusk mediated PAMP recognition and binding.

Scavenger receptors (SRs) are significant endocytic receptors contributing to constant internal environment. SR-cysteine-rich (SRCR) domain-containing SR is the most important class of SRs which has been so far reported exclusively in mammals and birds. In the present study, a novel SRCR domain-containing SR (CfSR) was firstly identified from scallop Chlamys farreri. The full-length cDNA of CfSR was of 2639 bp encoding a polypeptide of 804 amino acids with a signal peptide, six SRCR domains, a UPAR-like domain and a ShK toxin-like domain. All the SRCR domains contain highly conserved six cysteine residues to form three pairs of intradomain disulfide, among which SRCR-D5 was assumed to participate in ligand-binding. An attachment site of sequence CTTPLCN was found in UPAR-like domain, indicating CfSR was an anchor protein. This prediction was confirmed by its localization on the outer surface of hemocytes with immunofluorescence assay. The mRNA expression of CfSR was up-regulated significantly by the stimulations of lipopolysaccharides, peptidoglycan and β-glucan. A truncated CfSR (from V⁴⁵⁶ to T⁸⁰⁴) including SRCR-D5 was recombined and expressed in Escherichia coli, and the recombined protein displayed unique broad ligand-binding properties not only for acetylated low density lipoprotein (Ac-LDL) and dextran sulfate, but also for various pathogen associated molecular patterns, such as LPS, PGN, mannan and zymosan. All the results indicated that CfSR, the most primitive SR identified to date, was a versatile PRR involved in immune recognition, and the existence of functional SR might trace back to at least mollusk phylum.