6KI0

Crystal Structure of Human ASC-CARD

6KI0 の概要

• エントリーDOI: 10.2210/pdb6ki0/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900009
• 分子名称: Maltose/maltodextrin-binding periplasmic protein,Apoptosis-associated speck-like protein containing a CARD, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: death domain fold, immune system
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 104277.57

構造登録者

Xu, Z.H.,Jin, T.C. (登録日: 2019-07-16, 公開日: 2020-07-22, 最終更新日: 2023-11-22)

主引用文献

Xu, Z.,Zhou, Y.,Liu, M.,Ma, H.,Sun, L.,Zahid, A.,Chen, Y.,Zhou, R.,Cao, M.,Wu, D.,Zhao, W.,Li, B.,Jin, T.
Homotypic CARD-CARD interaction is critical for the activation of NLRP1 inflammasome.
Cell Death Dis, 12:57-57, 2021

PubMed Abstract: Cytosolic inflammasomes are supramolecular complexes that are formed in response to intracellular pathogens and danger signals. However, as to date, the detailed description of a homotypic caspase recruitment domain (CARD) interaction between NLRP1 and ASC has not been presented. We found the CARD-CARD interaction between purified NLRP1 and ASC experimentally and the filamentous supramolecular complex formation in an in vitro proteins solution. Moreover, we determined a high-resolution crystal structure of the death domain fold of the human ASC. Mutational and structural analysis revealed three conserved interfaces of the death domain superfamily (Type I, II, and III), which mediate the assembly of the NLRP1/ASC complex. In addition, we validated the role of the three major interfaces of CARDs in assembly and activation of NLRP1 inflammasome in vitro. Our findings suggest a Mosaic model of homotypic CARD interactions for the activation of NLRP1 inflammasome. The Mosaic model provides insights into the mechanisms of inflammasome assembly and signal transduction amplification.

PubMed: 33431827
DOI: 10.1038/s41419-020-03342-8

実験手法

X-RAY DIFFRACTION (2 Å)