Crystal structure of the leucine-rich repeat domain of the NOD-like receptor NLRP1: Implications for binding of muramyl dipeptide

The NOD-like receptor NLRP1 (NLR family, pyrin domain containing 1) senses the presence of the bacterial cell wall component L-muramyl dipeptide (MDP) inside the cell. We determined the crystal structure of the LRR domain of human NLRP1 in the absence of MDP to a resolution of 1.65 angstrom. The fold of the structure can be assigned to the ribonuclease inhibitor-like class of LRR proteins. We compared our structure with X-ray models of the LRR domains of NLRX1 and NLRC4 and a homology model of the LRR domain of NOD2. We conclude that the MDP binding site of NLRP1 is not located in the LRR domain. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.