PDBsum entry 6npy

Immune system

PDB id: 6npy

Contents

Protein chains

188 a.a.

813 a.a.

Ligands

ADP

PDB id:

6npy

Name:

Immune system

Title:

Cryo-em structure of nlrp3 bound to nek7

Structure:

Interferon-induced, double-stranded RNA-activated protein kinase,serine/threonine-protein kinase nek7. Chain: b. Synonym: eukaryotic translation initiation factor 2-alpha kinase 2, eif-2a protein kinase 2,interferon-inducible RNA-dependent protein kinase,p1/eif-2a protein kinase,protein kinase RNA-activated,pkr, protein kinase r,tyrosine-protein kinase eif2ak2,p68 kinase,never in mitosis a-related kinase 7,nima-related protein kinase 7. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: eif2ak2, pkr, prkr, nek7. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: nlrp3, c1orf7, cias1, nalp3, pypaf1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Authors:

H.Sharif,L.Wang,W.L.Wang,H.Wu

Key ref:

H.Sharif et al. (2019). Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome. Nature, 570, 338-343. PubMed id: 31189953 DOI: 10.1038/s41586-019-1295-z

Date:

18-Jan-19 Release date: 19-Jun-19

Protein chain

Q8TDX7  (NEK7_HUMAN) -  Serine/threonine-protein kinase Nek7 from Homo sapiens

Seq: 302 a.a.

Struc: 188 a.a.

Protein chain

Q96P20  (NLRP3_HUMAN) -  NACHT, LRR and PYD domains-containing protein 3 from Homo sapiens

Seq: 1036 a.a.

Struc: 813 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chain A: E.C.3.6.4.- - ?????
• Enzyme class 3: Chain B: E.C.2.7.11.34 - NEK6-subfamily protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/s41586-019-1295-z

Nature 570:338-343 (2019)

PubMed id: 31189953

Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome.

H.Sharif, L.Wang, W.L.Wang, V.G.Magupalli, L.Andreeva, Q.Qiao, A.V.Hauenstein, Z.Wu, G.Núñez, Y.Mao, H.Wu.

ABSTRACT

The NLRP3 inflammasome can be activated by stimuli that include nigericin, uric acid crystals, amyloid-β fibrils and extracellular ATP. The mitotic kinase NEK7 licenses the assembly and activation of the NLRP3 inflammasome in interphase. Here we report a cryo-electron microscopy structure of inactive human NLRP3 in complex with NEK7, at a resolution of 3.8 Å. The earring-shaped NLRP3 consists of curved leucine-rich-repeat and globular NACHT domains, and the C-terminal lobe of NEK7 nestles against both NLRP3 domains. Structural recognition between NLRP3 and NEK7 is confirmed by mutagenesis both in vitro and in cells. Modelling of an active NLRP3-NEK7 conformation based on the NLRC4 inflammasome predicts an additional contact between an NLRP3-bound NEK7 and a neighbouring NLRP3. Mutations to this interface abolish the ability of NEK7 or NLRP3 to rescue NLRP3 activation in NEK7-knockout or NLRP3-knockout cells. These data suggest that NEK7 bridges adjacent NLRP3 subunits with bipartite interactions to mediate the activation of the NLRP3 inflammasome.