5H8D

Crystal structure of an ASC binding nanobody

5H8D の概要

• エントリーDOI: 10.2210/pdb5h8d/pdb
• 関連するPDBエントリー: 5H8O
• 分子名称: VHH nanobody (2 entities in total)
• 機能のキーワード: vhh nanobody, asc-binding, antibody fragment, inflammasome, immune system
• 由来する生物種: Lama glama (llama)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12253.59

構造登録者

Lu, A.,Schmidt, F.I.,Ruan, J.,Tang, C.,Wu, H.,Ploegh, H.L. (登録日: 2015-12-23, 公開日: 2016-04-06, 最終更新日: 2024-11-06)

主引用文献

Schmidt, F.I.,Lu, A.,Chen, J.W.,Ruan, J.,Tang, C.,Wu, H.,Ploegh, H.L.
A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly.
J.Exp.Med., 213:771-790, 2016

PubMed Abstract: Myeloid cells assemble inflammasomes in response to infection or cell damage; cytosolic sensors activate pro-caspase-1, indirectly for the most part, via the adaptors ASC and NLRC4. This leads to secretion of proinflammatory cytokines and pyroptosis. To explore complex formation under physiological conditions, we generated an alpaca single domain antibody, VHHASC, which specifically recognizes the CARD of human ASC via its type II interface. VHHASC not only impairs ASC(CARD) interactions in vitro, but also inhibits inflammasome activation in response to NLRP3, AIM2, and NAIP triggers when expressed in living cells, highlighting a role of ASC in all three types of inflammasomes. VHHASC leaves the Pyrin domain of ASC functional and stabilizes a filamentous intermediate of inflammasome activation. Incorporation of VHHASC-EGFP into these structures allowed the visualization of endogenous ASC(PYD) filaments for the first time. These data revealed that cross-linking of ASC(PYD) filaments via ASC(CARD) mediates the assembly of ASC foci.

PubMed: 27069117
DOI: 10.1084/jem.20151790

実験手法

X-RAY DIFFRACTION (1.89 Å)