2NAQ

3D NMR solution structure of NLRP3 PYD

2NAQ の概要

• エントリーDOI: 10.2210/pdb2naq/pdb
• NMR情報: BMRB: 25943
• 分子名称: NACHT, LRR and PYD domains-containing protein 3 (1 entity in total)
• 機能のキーワード: death domain superfamily, apoptosis
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytosol : Q96P20
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10643.30

構造登録者

de Alba, E.,Oroz, J. (登録日: 2016-01-07, 公開日: 2016-07-27, 最終更新日: 2024-05-15)

主引用文献

Oroz, J.,Barrera-Vilarmau, S.,Alfonso, C.,Rivas, G.,de Alba, E.
ASC Pyrin Domain Self-associates and Binds NLRP3 Protein Using Equivalent Binding Interfaces.
J.Biol.Chem., 291:19487-19501, 2016

PubMed Abstract: Death domain superfamily members typically act as adaptors mediating in the assembly of supramolecular complexes with critical apoptosis and inflammation functions. These modular proteins consist of death domains, death effector domains, caspase recruitment domains, and pyrin domains (PYD). Despite the high structural similarity among them, only homotypic interactions participate in complex formation, suggesting that subtle factors differentiate each interaction type. It is thus critical to identify these factors as an essential step toward the understanding of the molecular basis of apoptosis and inflammation. The proteins apoptosis-associated speck-like protein containing a CARD (ASC) and NLRP3 play key roles in the regulation of apoptosis and inflammation through self-association and protein-protein interactions mediated by their PYDs. To better understand the molecular basis of their function, we have characterized ASC and NLRP3 PYD self-association and their intermolecular interaction by solution NMR spectroscopy and analytical ultracentrifugation. We found that ASC self-associates and binds NLRP3 PYD through equivalent protein regions, with higher binding affinity for the latter. These regions are located at opposite sides of the protein allowing multimeric complex formation previously shown in ASC PYD fibril assemblies. We show that NLRP3 PYD coexists in solution as a monomer and highly populated large-order oligomerized species. Despite this, we determined its monomeric three-dimensional solution structure by NMR and characterized its binding to ASC PYD. Using our novel structural data, we propose molecular models of ASC·ASC and ASC·NLRP3 PYD early supramolecular complexes, providing new insights into the molecular mechanisms of inflammasome and apoptosis signaling.

PubMed: 27432880
DOI: 10.1074/jbc.M116.741082

実験手法

SOLUTION NMR