This article is part of the Research Topic NLR-protein functions in immunity

Original Research ARTICLE

Front. Immunol., 07 October 2013 |

Comparative genomic and sequence analysis provides insight into the molecular functionality of NOD1 and NOD2

  • Department of Biochemistry, University of Cambridge, Cambridge, UK

Amino acids with functional or key structural roles display higher degrees of conservation through evolution. The comparative analysis of protein sequences from multiple species and/or between homologous proteins can be highly informative in the identification of key structural and functional residues. Residues which in turn provide insight into the molecular mechanisms of protein function. We have explored the genomic and amino acid conservation of the prototypic innate immune genes NOD1 and NOD2. NOD1 orthologs were found in all vertebrate species analyzed, whilst NOD2 was absent from the genomes of avian, reptilian and amphibian species. Evolutionary trace analysis was used to identify highly conserved regions of NOD1 and NOD2 across multiple species. Consistent with the known functions of NOD1 and NOD2 highly conserved patches were identified that matched the Walker A and B motifs and provided interaction surfaces for the adaptor protein RIP2. Other patches of high conservation reflect key structural functions as predicted by homology models. In addition, the pattern of residue conservation within the leucine-rich repeat (LRR) region of NOD1 and NOD2 is indicative of a conserved mechanism of ligand recognition involving the concave surface of the LRRs.

Keywords: NLR, NOD1/NOD2, comparative biology, evolutionary tracing, CARD, innate immunity, LRR

Citation: Boyle JP, Mayle S, Parkhouse R and Monie TP (2013) Comparative genomic and sequence analysis provides insight into the molecular functionality of NOD1 and NOD2. Front. Immunol. 4:317. doi: 10.3389/fimmu.2013.00317

Received: 27 July 2013; Paper pending published: 28 August 2013;
Accepted: 18 September 2013; Published online: 07 October 2013.

Edited by:

Thomas A. Kufer, University of Cologne, Germany

Reviewed by:

Annapurna Nayak, Brunel University, UK
Ivo G. Boneca, Institut Pasteur, France

Copyright: © 2013 Boyle, Mayle, Parkhouse and Monie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Tom P. Monie, Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK e-mail:

Sophie Mayle and Rhiannon Parkhouse have contributed equally to this work.