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- Title
Direct binding and internalization of diverse extracellular nucleic acid species through the collagenous domain of class A scavenger receptors.
- Authors
Baid, Kaushal; Huynh, Angela; Boulton, Stephen; Guarné, Alba; Mossman, Karen L; Melacini, Giuseppe; Nellimarla, Srinivas; Collins, Susan E
- Abstract
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 dsRNA, 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. Class A scavenger receptors have been implicated in the binding and uptake of circulating nucleic acids. Here, we show that the collagenous domain of class A scavenger receptors is sufficient to directly bind RNA and DNA species of different length, sequence and size. Furthermore, scavenger receptors are sufficient to mediate the binding and uptake of circulating RNA and DNA species.
- Subjects
NUCLEIC acids; SCAVENGER receptors (Biochemistry); ANTIVIRAL agents; INTERFERONS; CYSTEINE; DNA
- Publication
Immunology & Cell Biology, 2018, Vol 96, Issue 9, p922
- ISSN
0818-9641
- Publication type
Article
- DOI
10.1111/imcb.12052