4N1J

Crystal structures of NLRP14 pyrin domain reveal a conformational switch mechanism, regulating its molecular interactions

4N1J の概要

• エントリーDOI: 10.2210/pdb4n1j/pdb
• 関連するPDBエントリー: 4N1K 4N1L
• 分子名称: NACHT, LRR and PYD domains-containing protein 14, GLYCEROL (3 entities in total)
• 機能のキーワード: death domain fold, pyrin domain, nod-like receptor, signaling protein, protein binding, spermatogenesis, innate immunity
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 50086.59

構造登録者

Eibl, C.,Hessenberger, M.,Wenger, J.,Brandstetter, H. (登録日: 2013-10-04, 公開日: 2014-07-16, 最終更新日: 2024-11-06)

主引用文献

Eibl, C.,Hessenberger, M.,Wenger, J.,Brandstetter, H.
Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions.
Acta Crystallogr.,Sect.D, 70:2007-2018, 2014

PubMed 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.

PubMed: 25004977
DOI: 10.1107/S1399004714010311

実験手法

X-RAY DIFFRACTION (2.6 Å)