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Differential Peptidoglycan Recognition Assay Using Varied Surface Presentations.
- Source :
-
Journal of the American Chemical Society [J Am Chem Soc] 2020 Jun 24; Vol. 142 (25), pp. 10926-10930. Date of Electronic Publication: 2020 Jun 16. - Publication Year :
- 2020
-
Abstract
- Bacterial peptidoglycan (PG) is recognized by the human innate immune system to generate an appropriate response. To gain an appreciation of how this essential polymer is sensed, a surface plasmon resonance (SPR) assay using varied PG surface presentation was developed. PG derivatives were synthesized and immobilized on the surface at different positions on the molecule to assess effects of ligand orientation on the binding affinities of NOD-like receptors (NLRs). NLRP1 and NOD2 are cytosolic innate immune proteins known to generate an immune response to PG. Both possess conserved leucine rich repeat domains (LRR) as proposed sites of molecular recognition, though limited biochemical evidence exists regarding the mechanisms of PG recognition. Here direct biochemical evidence for the association of PG fragments to NOD2 and NLRP1 with nanomolar affinity is shown. The orientations in which the fragments were presented on the SPR surface influenced the strength of PG recognition by both NLRs. This assay displays fundamental differences in binding preferences for PG by innate immune receptors and reveals unique recognition mechanisms between the LRRs. Each receptor uses specific ligand structural features to achieve optimal binding, which will be critical information to manipulate these responses and combat diseases.
- Subjects :
- Acetylmuramyl-Alanyl-Isoglutamine analogs & derivatives
Amino Acid Sequence
Humans
Ligands
NLR Proteins
Protein Binding
Surface Plasmon Resonance
Acetylmuramyl-Alanyl-Isoglutamine metabolism
Adaptor Proteins, Signal Transducing metabolism
Apoptosis Regulatory Proteins metabolism
Nod2 Signaling Adaptor Protein metabolism
Peptidoglycan chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5126
- Volume :
- 142
- Issue :
- 25
- Database :
- MEDLINE
- Journal :
- Journal of the American Chemical Society
- Publication Type :
- Academic Journal
- Accession number :
- 32520538
- Full Text :
- https://doi.org/10.1021/jacs.0c03933