The Innate Immune Protein Nod2 Binds Directly to MDP, a Bacterial Cell Wall

ABSTRACT: Mammalian Nod2 is an intracellular protein that is implicated in the innate immune response to the bacterial cell wall and is associated with the development of Crohn’s disease, Blau syndrome, and gastrointestinal cancers. Nod2 is required for an immune response to muramyl dipeptide (MDP), an immunostimulatory frag-ment of bacterial cell wall, but it is not known whether MDP binds directly to Nod2. We report the expression and purification of human Nod2 from insect cells. Using novel MDP self-assembled monolayers (SAMs), we provide the first biochemical evidence for a direct, high-affinity interaction between Nod2 and MDP. The innate immune system is the body’s first line of defenseagainst invading pathogens.1,2 This ancient system has evolved to exist in a symbiotic relationship with commensal bacteria and at the same time to recognize and destroy virulen