The three-dimensional structure and recognition mechanism of Manduca sexta peptidoglycan recognition protein-1
[1];
- Oklahoma State Univ., Stillwater, OK (United States)
- Univ. of Georgia, Athens, GA (United States). Complex Carbohydrate Research Center
- Univ. of Georgia, Athens, GA (United States). Complex Carbohydrate Research Center; Univ. of Utrecht (Netherlands). Chemical Biology and Drug Discovery, Utrecht Inst. for Pharmaceutical Sciences, Bijvoet Center for Biomolecular Research
Peptidoglycan recognition proteins (PGRPs) recognize bacteria through their unique cell wall constituent, peptidoglycans (PGs). PGRPs are conserved from insects to mammals and all function in antibacterial defense. In the tobacco hornworm Manduca sexta, PGRP1 and microbe binding protein (MBP) interact with PGs and hemolymph protease-14 precursor (proHP14) to yield active HP14. HP14 triggers a serine protease network that produces active phenoloxidase (PO), Spätzle, and other cytokines to stimulate immune responses. PGRP1 binds preferentially to diaminopimelic acid (DAP)-PGs of Gram-negative bacteria and Gram-positive Bacillus and Clostridium species than Lys-PGs of other Gram-positive bacteria. In this study, we synthesized DAP- and Lys-muramyl pentapeptide (MPP) and monitored their associations with M. sexta PGRP1 by surface plasmon resonance. The Kd values (0.57 μM for DAP-MPP and 45.6 μM for Lys-MPP) agree with the differential recognition of DAP- and Lys-PGs. To reveal its structural basis, we produced the PGRP1 in insect cells and determined its structure at a resolution of 2.1 Å. The protein adopts a fold similar to those from other PGRPs with a classical L-shaped PG-binding groove. A unique loop lining the shallow groove suggests a different ligand-binding mechanism. In summary, this study provided new insights into the PG recognition by PGRPs, a critical first step that initiates the serine protease cascade.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- National Institutes of Health (NIH); USDOE
- Grant/Contract Number:
- AI112662; GM58634
- OSTI ID:
- 1515294
- Journal Information:
- Insect Biochemistry and Molecular Biology, Vol. 108, Issue C; ISSN 0965-1748
- Country of Publication:
- United States
- Language:
- ENGLISH
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