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

FEBS Lett. 2014 Sep 17;588(18):3327-32. doi: 10.1016/j.febslet.2014.07.017. Epub 2014 Jul 24.

Abstract

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 1.65Å. 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.

Keywords: Muramyl dipeptide; NALP1; NLR family pyrin domain containing 1; NOD-like receptor; Pathogen associated molecular pattern.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / chemistry*
  • Adaptor Proteins, Signal Transducing / chemistry*
  • Amino Acid Motifs
  • Apoptosis Regulatory Proteins / chemistry*
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • NLR Proteins
  • Protein Binding
  • Protein Structure, Tertiary
  • Repetitive Sequences, Amino Acid
  • Structural Homology, Protein

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • NLR Proteins
  • NLRP1 protein, human
  • Acetylmuramyl-Alanyl-Isoglutamine

Associated data

  • PDB/4IM6