LRRsearch: An asynchronous server-based application for the prediction of leucine-rich repeat motifs and an integrative database of NOD-like receptors

The leucine-rich repeat (LRR) motifs of the nucleotide-binding oligomerization domain like receptors (NLRs) play key roles in recognizing and binding various pathogen associated molecular patterns (PAMPs) resulting in the activation of downstream signaling and innate immunity. Therefore, identification of LRR motifs is very important to study ligand-receptor interaction. To date, available resources pose restrictions including both false negative and false positive prediction of LRR motifs from the primary protein sequence as their algorithms are relied either only on sequence based comparison or alignment techniques or are over biased for a particular LRR containing protein family. Therefore, to minimize the error (≤5%) and to identify a maximum number of LRR motifs in the wide range of proteins, we have developed "LRRsearch" web-server using position specific scoring matrix (PSSM) of 11 residue LRR-HCS (highly conserved segment) which are frequently observed motifs in the most divergent classes of LRR containing proteins. A data library of 421 proteins, distributed among five known NLR families has also been integrated with the "LRRsearch" for the rich user experience. The access to the "LRRsearch" program is freely available at http://www.lrrsearch.com/.

[1]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[2]  Amos Bairoch,et al.  ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins , 2006, Nucleic Acids Res..

[3]  P ? ? ? ? ? ? ? % ? ? ? ? , 1991 .

[4]  Peer Bork,et al.  SMART 7: recent updates to the protein domain annotation resource , 2011, Nucleic Acids Res..

[5]  Alex Bateman,et al.  InterPro: An Integrated Documentation Resource for Protein Families, Domains and Functional Sites , 2002, Briefings Bioinform..

[6]  Rodrigo Lopez,et al.  Clustal W and Clustal X version 2.0 , 2007, Bioinform..

[7]  Y. Kuroki,et al.  Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors , 2007, BMC Genomics.

[8]  Bikash R. Sahoo,et al.  Identification of MDP (muramyl dipeptide)-binding key domains in NOD2 (nucleotide-binding and oligomerization domain-2) receptor of Labeo rohita , 2012, Fish Physiology and Biochemistry.

[9]  Edmond Godfroid,et al.  Distantly related lipocalins share two conserved clusters of hydrophobic residues: use in homology modeling. , 2008, BMC structural biology.

[10]  D. Vaux,et al.  Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs , 2001, Genome Biology.

[11]  P. Bucher,et al.  The CARD domain: a new apoptotic signalling motif. , 1997, Trends in biochemical sciences.

[12]  S. K. Pradhan,et al.  Structural insights into the MDP binding and CARD–CARD interaction in zebrafish (Danio rerio) NOD2: a molecular dynamics approach , 2014, Journal of molecular recognition : JMR.

[13]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[14]  Ying Gao,et al.  Bioinformatics Applications Note Sequence Analysis Cd-hit Suite: a Web Server for Clustering and Comparing Biological Sequences , 2022 .

[15]  D. Philpott,et al.  Nod-like proteins in immunity, inflammation and disease , 2006, Nature Immunology.

[16]  S. K. Pradhan,et al.  A conformational analysis of mouse Nalp3 domain structures by molecular dynamics simulations, and binding site analysis. , 2014, Molecular bioSystems.

[17]  L. Holm,et al.  The Pfam protein families database , 2005, Nucleic Acids Res..

[18]  G. Núñez,et al.  Cell death and immunity: NODs: intracellular proteins involved in inflammation and apoptosis , 2003, Nature Reviews Immunology.

[19]  F. Martinon,et al.  The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation , 2001, Current Biology.

[20]  S. Akira,et al.  Pathogen Recognition and Innate Immunity , 2006, Cell.

[21]  Adam Godzik,et al.  Clustering of highly homologous sequences to reduce the size of large protein databases , 2001, Bioinform..

[22]  E. Koonin,et al.  The NACHT family - a new group of predicted NTPases implicated in apoptosis and MHC transcription activation. , 2000, Trends in biochemical sciences.

[23]  D. Werling,et al.  LRRfinder: a web application for the identification of leucine-rich repeats and an integrative Toll-like receptor database. , 2010, Developmental and comparative immunology.

[24]  A. Iwasaki Innate immune recognition of HIV-1. , 2012, Immunity.

[25]  Shaila C. Rössle,et al.  LRRML: a conformational database and an XML description of leucine-rich repeats (LRRs) , 2008, BMC Structural Biology.

[26]  Elspeth A. Bruford,et al.  Genenames.org: the HGNC resources in 2013 , 2012, Nucleic Acids Res..

[27]  J. Bertin,et al.  The PYRIN domain: a novel motif found in apoptosis and inflammation proteins , 2000, Cell Death and Differentiation.

[28]  M. Chamaillard,et al.  NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. , 2005, Annual review of biochemistry.

[29]  Adam Godzik,et al.  Tolerating some redundancy significantly speeds up clustering of large protein databases , 2002, Bioinform..

[30]  Alex Bateman,et al.  InterPro : An integrated documentation resource for protein families , domains and functional sites The InterPro Consortium : , 2005 .

[31]  Adam Godzik,et al.  Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences , 2006, Bioinform..

[32]  Bikash R. Sahoo,et al.  Activation of Nucleotide-Binding Oligomerization Domain 1 (NOD1) Receptor Signaling in Labeo rohita by iE-DAP and Identification of Ligand-Binding Key Motifs in NOD1 by Molecular Modeling and Docking , 2013, Applied Biochemistry and Biotechnology.

[33]  Ana M. Rojas,et al.  The Nod-Like Receptor (NLR) Family: A Tale of Similarities and Differences , 2008, PloS one.

[34]  D. Davies,et al.  Leucine-rich repeats and pathogen recognition in Toll-like receptors. , 2003, Trends in immunology.

[35]  C. Janeway,et al.  An ancient system of host defense. , 1998, Current opinion in immunology.

[36]  Bikash R. Sahoo,et al.  Structural insights of rohu TLR3, its binding site analysis with fish reovirus dsRNA, poly I:C and zebrafish TRIF. , 2012, International journal of biological macromolecules.

[37]  B. Kobe,et al.  The leucine-rich repeat as a protein recognition motif. , 2001, Current opinion in structural biology.

[38]  M. Nei,et al.  MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. , 2011, Molecular biology and evolution.

[39]  Shizuo Akira,et al.  Toll-like receptor signalling , 2004, Nature Reviews Immunology.

[40]  R. Agarwala,et al.  Protein database searches using compositionally adjusted substitution matrices , 2005, The FEBS journal.

[41]  Charless C. Fowlkes,et al.  Three-dimensional morphology and gene expression in the Drosophila blastoderm at cellular resolution I: data acquisition pipeline , 2006, Genome Biology.