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Understanding the molecular differential recognition of muramyl peptide ligands by LRR domains of human NOD receptors.
Vijayrajratnam, Sukhithasri; Pushkaran, Anju Choorakottayil; Balakrishnan, Aathira; Vasudevan, Anil Kumar; Biswas, Raja; Mohan, Chethampadi Gopi.
Afiliación
  • Vijayrajratnam S; Center for Nanosciences and Molecular Medicine, Amrita University, Kochi, Kerala 682041, India.
  • Pushkaran AC; Center for Nanosciences and Molecular Medicine, Amrita University, Kochi, Kerala 682041, India.
  • Balakrishnan A; Center for Nanosciences and Molecular Medicine, Amrita University, Kochi, Kerala 682041, India.
  • Vasudevan AK; Department of Microbiology, Amrita Institute of Medical Sciences and Research Center, Amrita University, Kochi, Kerala 682041, India.
  • Biswas R; Center for Nanosciences and Molecular Medicine, Amrita University, Kochi, Kerala 682041, India rajabiswas@aims.amrita.edu cgmohan@aims.amrita.edu.
  • Mohan CG; Center for Nanosciences and Molecular Medicine, Amrita University, Kochi, Kerala 682041, India rajabiswas@aims.amrita.edu cgmohan@aims.amrita.edu.
Biochem J ; 474(16): 2691-2711, 2017 07 27.
Article en En | MEDLINE | ID: mdl-28673961
Human nucleotide-binding oligomerization domain proteins, hNOD1 and hNOD2, are host intracellular receptors with C-terminal leucine-rich repeat (LRR) domains, which recognize specific bacterial peptidoglycan (PG) fragments as their ligands. The specificity of this recognition is dependent on the third amino acid of the stem peptide of the PG ligand, which is usually meso-diaminopimelic acid (mesoDAP) or l-lysine (l-Lys). Since the LRR domains of hNOD receptors had been experimentally shown to confer the PG ligand-sensing specificity, we developed three-dimensional structures of hNOD1-LRR and the hNOD2-LRR to understand the mechanism of differential recognition of muramyl peptide ligands by hNOD receptors. The hNOD1-LRR and hNOD2-LRR receptor models exhibited right-handed curved solenoid shape. The hot-spot residues experimentally proved to be critical for ligand recognition were located in the concavity of the NOD-LRR and formed the recognition site. Our molecular docking analyses and molecular electrostatic potential mapping studies explain the activation of hNOD-LRRs, in response to effective molecular interactions of PG ligands at the recognition site; and conversely, the inability of certain PG ligands to activate hNOD-LRRs, by deviations from the recognition site. Based on molecular docking studies using PG ligands, we propose few residues - G825, D826 and N850 in hNOD1-LRR and L904, G905, W931, L932 and S933 in hNOD2-LRR, evolutionarily conserved across different host species, which may play a major role in ligand recognition. Thus, our integrated experimental and computational approach elucidates the molecular basis underlying the differential recognition of PG ligands by hNOD receptors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilmuramil-Alanil-Isoglutamina / Proteína Adaptadora de Señalización NOD1 / Proteína Adaptadora de Señalización NOD2 / Simulación del Acoplamiento Molecular Límite: Humans Idioma: En Revista: Biochem J Año: 2017 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilmuramil-Alanil-Isoglutamina / Proteína Adaptadora de Señalización NOD1 / Proteína Adaptadora de Señalización NOD2 / Simulación del Acoplamiento Molecular Límite: Humans Idioma: En Revista: Biochem J Año: 2017 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido