2KM6

NMR structure of the NLRP7 Pyrin domain

Summary for 2KM6

• Entry DOI: 10.2210/pdb2km6/pdb
• NMR Information: BMRB: 16263
• Descriptor: NACHT, LRR and PYD domains-containing protein 7 (1 entity in total)
• Functional Keywords: nlrp7, pyrin domain, innate immune system, nalp, atp-binding, disease mutation, leucine-rich repeat, nucleotide-binding, immune system, signaling protein, protein binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 12361.92

Authors

Pinheiro, A.,Proell, M.,Schwarzenbacher, R.,Peti, W. (deposition date: 2009-07-21, release date: 2010-06-09, Last modification date: 2024-05-08)

Primary citation

Pinheiro, A.S.,Proell, M.,Eibl, C.,Page, R.,Schwarzenbacher, R.,Peti, W.
Three-dimensional structure of the NLRP7 pyrin domain: insight into pyrin-pyrin-mediated effector domain signaling in innate immunity.
J.Biol.Chem., 285:27402-27410, 2010

PubMed Abstract: The innate immune system provides an initial line of defense against infection. Nucleotide-binding domain- and leucine-rich repeat-containing protein (NLR or (NOD-like)) receptors play a critical role in the innate immune response by surveying the cytoplasm for traces of intracellular invaders and endogenous stress signals. NLRs themselves are multi-domain proteins. Their N-terminal effector domains (typically a pyrin or caspase activation and recruitment domain) are responsible for driving downstream signaling and initiating the formation of inflammasomes, multi-component complexes necessary for cytokine activation. However, the currently available structures of NLR effector domains have not yet revealed the mechanism of their differential modes of interaction. Here, we report the structure and dynamics of the N-terminal pyrin domain of NLRP7 (NLRP7 PYD) obtained by NMR spectroscopy. The NLRP7 PYD adopts a six-alpha-helix bundle death domain fold. A comparison of conformational and dynamics features of the NLRP7 PYD with other PYDs showed distinct differences for helix alpha3 and loop alpha2-alpha3, which, in NLRP7, is stabilized by a strong hydrophobic cluster. Moreover, the NLRP7 and NLRP1 PYDs have different electrostatic surfaces. This is significant, because death domain signaling is driven by electrostatic contacts and stabilized by hydrophobic interactions. Thus, these results provide new insights into NLRP signaling and provide a first molecular understanding of inflammasome formation.

PubMed: 20547486
DOI: 10.1074/jbc.M110.113191

Experimental method

SOLUTION NMR