PDBsum entry 2km6

Signaling protein, protein binding

PDB id: 2km6

Contents

Protein chain

96 a.a. *

* Residue conservation analysis

PDB id:

2km6

Name:

Signaling protein, protein binding

Title:

Nmr structure of the nlrp7 pyrin domain

Structure:

Nacht, lrr and pyd domains-containing protein 7. Chain: a. Synonym: pyrin-containing apaf1-like protein 3, nucleotide-binding oligomerization domain protein 12. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nlrp7, nalp7, nod12, pypaf3. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

A.Pinheiro,M.Proell,R.Schwarzenbacher,W.Peti

Key ref:

A.S.Pinheiro et al. (2010). 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. PubMed id: 20547486

Date:

21-Jul-09 Release date: 09-Jun-10

Protein chain

Q8WX94  (NALP7_HUMAN) -  NACHT, LRR and PYD domains-containing protein 7 from Homo sapiens

Seq: 980 a.a.

Struc: 96 a.a.

J Biol Chem 285:27402-27410 (2010)

PubMed id: 20547486

Three-dimensional structure of the NLRP7 pyrin domain: insight into pyrin-pyrin-mediated effector domain signaling in innate immunity.

A.S.Pinheiro, M.Proell, C.Eibl, R.Page, R.Schwarzenbacher, W.Peti.

ABSTRACT

The innate immune system provides an initial line of defense against infection. NLR (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 CARD 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 6 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, as 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.