4GF9

Structural insights into the dual strategy of recognition of peptidoglycan recognition protein, PGRP-S: ternary complex of PGRP-S with LPS and fatty acid

Summary for 4GF9

• Entry DOI: 10.2210/pdb4gf9/pdb
• Descriptor: Peptidoglycan recognition protein 1, STEARIC ACID, (R)-((2R,3S,4R,5R,6R)-3-HYDROXY-2-(HYDROXYMETHYL)-5-((R)-3-HYDROXYTETRADECANAMIDO)-6-(PHOSPHONOOXY)TETRAHYDRO-2H-PYRAN-4-YL) 3-HYDROXYTETRADECANOATE, ... (5 entities in total)
• Functional Keywords: peptidoglycan binding, immune response, secreted, antimicrobial, pgrp, antibiotic, antimicrobial protein
• Biological source: Camelus dromedarius (camel,dromedaries,dromedary,one-humped camel)
• Cellular location: Secreted (By similarity): Q9GK12
• Total number of polymer chains: 4
• Total formula weight: 77134.27

Authors

Sharma, P.,Dube, D.,Sinha, M.,Yadav, S.,Kaur, P.,Sharma, S.,Singh, T.P. (deposition date: 2012-08-03, release date: 2012-09-26, Last modification date: 2023-09-13)

Primary citation

Sharma, P.,Dube, D.,Sinha, M.,Yadav, S.,Kaur, P.,Sharma, S.,Singh, T.P.
Structural insights into the dual strategy of recognition by peptidoglycan recognition protein, PGRP-S: structure of the ternary complex of PGRP-S with lipopolysaccharide and stearic acid.
Plos One, 8:e53756-e53756, 2013

PubMed Abstract: Peptidoglycan recognition proteins (PGRPs) are part of the innate immune system. The 19 kDa Short PGRP (PGRP-S) is one of the four mammalian PGRPs. The concentration of PGRP-S in camel (CPGRP-S) has been shown to increase considerably during mastitis. The structure of CPGRP-S consists of four protein molecules designated as A, B, C and D forming stable intermolecular contacts, A-B and C-D. The A-B and C-D interfaces are located on the opposite sides of the same monomer leading to the the formation of a linear chain with alternating A-B and C-D contacts. Two ligand binding sites, one at C-D contact and another at A-B contact have been observed. CPGRP-S binds to the components of bacterial cell wall molecules such as lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN) from both gram-positive and gram-negative bacteria. It also binds to fatty acids including mycolic acid of the Mycobacterium tuberculosis (Mtb). Previous structural studies of binary complexes of CPGRP-S with LPS and stearic acid (SA) have shown that LPS binds to CPGRP-S at C-D contact (Site-1) while SA binds to it at the A-B contact (Site-2). The binding studies using surface plasmon resonance showed that LPS and SA bound to CPGRP-S in the presence of each other. The structure determination of the ternary complex showed that LPS and SA bound to CPGRP-S at Site-1 and Site-2 respectively. LPS formed 13 hydrogen bonds and 159 van der Waals contacts (distances ≤4.2 Å) while SA formed 56 van der Waals contacts. The ELISA test showed that increased levels of productions of pro-inflammatory cytokines TNF-α and IFN-γ due to LPS and SA decreased considerably upon the addition of CPGRP-S.

PubMed: 23326499
DOI: 10.1371/journal.pone.0053756

Experimental method

X-RAY DIFFRACTION (2.8 Å)