Premium
Direct binding and internalization of diverse extracellular nucleic acid species through the collagenous domain of class A scavenger receptors
Author(s) -
Baid Kaushal,
Nellimarla Srinivas,
Huynh Angela,
Boulton Stephen,
Guarné Alba,
Melacini Giuseppe,
Collins Susan E,
Mossman Karen L
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12052
Subject(s) - nucleic acid , scavenger receptor , internalization , receptor , biology , rna , biochemistry , pattern recognition receptor , dna , extracellular , recombinant dna , microbiology and biotechnology , innate immune system , gene , lipoprotein , cholesterol
Nucleic acids are potential pathogen‐associated or danger‐associated molecular patterns that modulate immune responses and the development of autoimmune disorders. Class A scavenger receptors (SR‐As) are a diverse group of pattern recognition receptors that recognize a variety of polyanionic ligands including nucleic acids. While SR ‐As are important for the recognition and internalization of extracellular ds RNA , little is known about extracellular DNA , despite its association with chronic infections and autoimmune disorders. In this study, we investigated the specificity of and requirement for SR ‐As in binding and internalizing different species, sequences and lengths of nucleic acids. We purified recombinant coiled‐coil/collagenous and scavenger receptor cysteine‐rich ( SRCR ) domains that have been implicated as potential ligand‐binding domains. We detected a direct interaction of RNA and DNA species with the coiled‐coil/collagenous domain, but not the SRCR domain. Despite the presence of additional surface receptors that bind nucleic acids, SR ‐As were found to be sufficient for nucleic acid binding and uptake in A549 human lung epithelial cells. Moreover, these findings suggest that the coiled‐coil/collagenous domain of SR ‐As is sufficient to bind nucleic acids independent of species, sequence or length.