Publication Type : Journal Article
Thematic Areas : Medical Sciences, Nanosciences and Molecular Medicine
Publisher : Biochem J.
Source : Biochem J, Volume 473, Issue 24, p.4573-4592 (2016)
Url : http://dx.doi.org/10.1042/bcj20160817
Keywords : amino acid sequence, Diaminopimelic Acid, Humans, Molecular Dynamics Simulation, Molecular Sequence Data, Nod1 Signaling Adaptor Protein, peptidoglycan, Protein Binding, Protein Structure, Secondary
Campus : Kochi
School : Center for Nanosciences, School of Medicine
Center : Amrita Center for Nanosciences and Molecular Medicine Move, Nanosciences
Department : Nanosciences and Molecular Medicine, Microbiology
Year : 2016
Abstract : Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is an intracellular pattern recognition receptor that recognizes bacterial peptidoglycan (PG) containing meso-diaminopimelic acid (mesoDAP) and activates the innate immune system. Interestingly, a few pathogenic and commensal bacteria modify their PG stem peptide by amidation of mesoDAP (mesoDAP). In the present study, NOD1 stimulation assays were performed using bacterial PG containing mesoDAP (PG) and mesoDAP (PG) to understand the differences in their biomolecular recognition mechanism. PG was effectively recognized, whereas PG showed reduced recognition by the NOD1 receptor. Restimulation of the NOD1 receptor, which was initially stimulated with PG using PG, did not show any further NOD1 activation levels than with PG alone. But the NOD1 receptor initially stimulated with PG responded effectively to restimulation with PG The biomolecular structure-recognition relationship of the ligand-sensing leucine-rich repeat (LRR) domain of human NOD1 (NOD1-LRR) with PG and PG was studied by different computational techniques to further understand the molecular basis of our experimental observations. The d-Glu-mesoDAP motif of GMTP, which is the minimum essential motif for NOD1 activation, was found involved in specific interactions at the recognition site, but the interactions of the corresponding d-Glu-mesoDAP motif of PG occur away from the recognition site of the NOD1 receptor. Hot-spot residues identified for effective PG recognition by NOD1-LRR include W820, G821, D826 and N850, which are evolutionarily conserved across different host species. These integrated results thus successfully provided the atomic level and biochemical insights on how PGs containing mesoDAP evade NOD1-LRR receptor recognition.
Cite this Research Publication : Sukhithasri Vijayrajratnam, Anju Choorakottayil Pushkaran, Aathira Balakrishnan, Anil Kumar Vasudevan, Raja Biswas, Chethampadi Gopi Mohan "Bacterial peptidoglycan with amidated meso-diaminopimelic acid evades NOD1 recognition: an insight into NOD1 structure–recognition", Biochemical Journal, 2017