Linked Life Data

21757725

Source:http://linkedlifedata.com/resource/pubmed/id/21757725

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2011-8-29
pubmed:abstractText
The oligopeptide transporter PepT1 expressed in inflamed colonic epithelial cells transports small bacterial peptides, such as muramyl dipeptide (MDP) and l-Ala-?-D-Glu-meso-diaminopimelic acid (Tri-DAP) into cells. The innate immune system uses various proteins to sense pathogen-associated molecular patterns. Nucleotide-binding oligomerization domain (NOD)-like receptors of which there are more than 20 related family members are present in the cytosol and recognize intracellular ligands. NOD proteins mediate NF-?B activation via receptor-interacting serine/threonine-protein kinase 2 (RICK or RIPK). The specific ligands for some NOD-like receptors have been identified. NOD type 1 (NOD1) is activated by peptides that contain a diaminophilic acid, such as the PepT1 substrate Tri-DAP. In other words, PepT1 transport activity plays an important role in controlling intracellular loading of ligands for NOD1 in turn determining the activation level of downstream inflammatory pathways. However, no direct interaction between Tri-DAP and NOD1 has been identified. In the present work, surface plasmon resonance and atomic force microscopy experiments showed direct binding between NOD1 and Tri-DAP with a K(d) value of 34.5 ?M. In contrast, no significant binding was evident between muramyl dipeptide and NOD1. Furthermore, leucine-rich region (LRR)-truncated NOD1 did not interact with Tri-DAP, indicating that Tri-DAP interacts with the LRR domain of NOD1. Next, we examined binding between RICK and NOD1 proteins and found that such binding was significant with a K(d) value of 4.13 ?M. However, NOD1/RICK binding was of higher affinity (K(d) of 3.26 ?M) when NOD1 was prebound to Tri-DAP. Furthermore, RICK phosphorylation activity was increased when NOD was prebound to Tri-DAP. In conclusion, we have shown that Tri-DAP interacts directly with the LRR domain of NOD1 and consequently increases RICK/NOD1 association and RICK phosphorylation activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31003-13
pubmed:dateRevised
2011-11-4
pubmed:meshHeading
pubmed-meshheading:21757725-Biophysics, pubmed-meshheading:21757725-Caco-2 Cells, pubmed-meshheading:21757725-Diaminopimelic Acid, pubmed-meshheading:21757725-Humans, pubmed-meshheading:21757725-Immunity, Innate, pubmed-meshheading:21757725-Inflammation, pubmed-meshheading:21757725-Leucine, pubmed-meshheading:21757725-Microscopy, Atomic Force, pubmed-meshheading:21757725-Nod1 Signaling Adaptor Protein, pubmed-meshheading:21757725-Nucleotides, pubmed-meshheading:21757725-Oligopeptides, pubmed-meshheading:21757725-Peptides, pubmed-meshheading:21757725-Phosphorylation, pubmed-meshheading:21757725-Protein Binding, pubmed-meshheading:21757725-Protein Structure, Tertiary, pubmed-meshheading:21757725-RNA, Small Interfering, pubmed-meshheading:21757725-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2011
pubmed:articleTitle
L-Ala-?-D-Glu-meso-diaminopimelic acid (DAP) interacts directly with leucine-rich region domain of nucleotide-binding oligomerization domain 1, increasing phosphorylation activity of receptor-interacting serine/threonine-protein kinase 2 and its interaction with nucleotide-binding oligomerization domain 1.
pubmed:affiliation
Department of Medicine, Division of Digestive Diseases, Emory University, Atlanta, Georgia 30322, USA. hlaroui@emory.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural