PDBsum entry 4n1k

Signaling protein

PDB id: 4n1k

Contents

Protein chains

88 a.a.

94 a.a.

Waters ×13

PDB id:

4n1k

Name:

Signaling protein

Title:

Crystal structures of nlrp14 pyrin domain reveal a conformational switch mechanism, regulating its molecular interactions

Structure:

Nacht, lrr and pyd domains-containing protein 14. Chain: a, b, c, d. Fragment: unp residues 1-100. Synonym: nucleotide-binding oligomerization domain protein 5. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nlrp14, nalp14, nod5. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

3.00Å R-factor: 0.216 R-free: 0.268

Authors:

C.Eibl,M.Hessenberger,J.Wenger,H.Brandstetter

Key ref:

C.Eibl et al. (2014). Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions. Acta Crystallogr D Biol Crystallogr, 70, 2007-2018. PubMed id: 25004977 DOI: 10.1107/S1399004714010311

Date:

04-Oct-13 Release date: 16-Jul-14

Protein chains

Q86W24  (NAL14_HUMAN) -  NACHT, LRR and PYD domains-containing protein 14 from Homo sapiens

Seq: 1093 a.a.

Struc: 88 a.a.*

Protein chain

Q86W24  (NAL14_HUMAN) -  NACHT, LRR and PYD domains-containing protein 14 from Homo sapiens

Seq: 1093 a.a.

Struc: 94 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1107/S1399004714010311

Acta Crystallogr D Biol Crystallogr 70:2007-2018 (2014)

PubMed id: 25004977

Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions.

C.Eibl, M.Hessenberger, J.Wenger, H.Brandstetter.

ABSTRACT

The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed.