Universität zu Köln

Mayle, Sophie, Boyle, Joseph P., Sekine, Eiki ORCID: 0000-0001-6555-7879, Zurek, Birte, Kufer, Thomas A. and Monie, Tom P. (2014). Engagement of Nucleotide-binding Oligomerization Domain-containing Protein 1 (NOD1) by Receptor-interacting Protein 2 (RIP2) Is Insufficient for Signal Transduction. J. Biol. Chem., 289 (33). S. 22900 - 22915. ROCKVILLE: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

Full text not available from this repository.

Abstract

Following activation, the cytoplasmic pattern recognition receptor nucleotide-binding oligomerization domain-containing protein 1 (NOD1) interacts with its adaptor protein receptor-interacting protein 2 (RIP2) to propagate immune signaling and initiate a proinflammatory immune response. This interaction is mediated by the caspase recruitment domain (CARD) of both proteins. Polymorphisms in immune proteins can affect receptor function and predispose individuals to specific autoinflammatory disorders. In this report, we show that mutations in helix 2 of the CARD of NOD1 disrupted receptor function but did not interfere with RIP2 interaction. In particular, N43S, a rare polymorphism, resulted in receptor dysfunction despite retaining normal cellular localization, protein folding, and an ability to interact with RIP2. Mutation of Asn-43 resulted in an increased tendency to form dimers, which we propose is the source of this dysfunction. We also demonstrate that mutation of Lys-443 and Tyr-474 in RIP2 disrupted the interaction with NOD1. Mapping the key residues involved in the interaction between NOD1 and RIP2 to the known structures of CARD complexes revealed the likely involvement of both type I and type III interfaces in the NOD1.RIP2 complex. Overall we demonstrate that the NOD1-RIP2 signaling axis is more complex than previously assumed, that simple engagement of RIP2 is insufficient to mediate signaling, and that the interaction between NOD1 and RIP2 constitutes multiple CARD-CARD interfaces.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mayle, Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Boyle, Joseph P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sekine, Eiki UNSPECIFIED orcid.org/0000-0001-6555-7879 UNSPECIFIED Zurek, Birte UNSPECIFIED UNSPECIFIED UNSPECIFIED Kufer, Thomas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Monie, Tom P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-431958
DOI:	10.1074/jbc.M114.557900
Journal or Publication Title:	J. Biol. Chem.
Volume:	289
Number:	33
Page Range:	S. 22900 - 22915
Date:	2014
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STRUCTURAL BASIS; CRYSTAL-STRUCTURE; ACTIVATION; RECRUITMENT; RECOGNITION; MECHANISM; RESPONSES; FILAMENT; MEMBRANE; ERBIN Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43195