EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 8974, Year 2024
掲載日	2024年10月17日
著者	Chao-Yu Yang / Yi-Chun Tseng / Yi-Fan Tu / Bai-Jiun Kuo / Li-Chung Hsu / Chia-I Lien / You-Sheng Lin / Yin-Ting Wang / Yen-Chen Lu / Tsung-Wei Su / Yu-Chih Lo / Su-Chang Lin /
PubMed 要旨	cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high ...cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes. Here we report the crystal plus cryo-EM structures to uncover an unconventional mechanism where cFLIP and procaspase-8 autonomously form a binary tandem DED complex, independent of FADD. This complex gains the ability to recruit FADD, thereby allosterically modulating cFLIP assembly and partially activating caspase-8 for RIPK1 cleavage. Our structure-guided mutagenesis experiments provide critical insights into these regulatory mechanisms, elucidating the resistance to apoptosis and necroptosis in achieving immortality. Finally, this research offers a unified model for the intricate bidirectional hierarchy-based processes using multiprotein helical assembly to govern cell fate decisions.
リンク	Nat Commun / PubMed:39419969 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.09 - 3.97 Å
構造データ	39424 8yni EMDB-39424, PDB-8yni: Structure of the FADD/Caspase-8/cFLIP death effector domain assembly 手法: EM (単粒子) / 解像度: 3.66 Å 39425 8ynk EMDB-39425, PDB-8ynk: Structure of the Caspase-8/cFLIP death effector domain assembly 手法: EM (単粒子) / 解像度: 3.62 Å 39426 8ynl EMDB-39426, PDB-8ynl: Structure of the Caspase-8/cFLIP death effector domain assembly 手法: EM (単粒子) / 解像度: 3.55 Å 39427 8ynm EMDB-39427, PDB-8ynm: Structure of the Caspase-8/cFLIP death effector domain assembly 手法: EM (単粒子) / 解像度: 3.49 Å 39428 8ynn EMDB-39428, PDB-8ynn: Structure of the Caspase-8/cFLIP death effector domain assembly 手法: EM (単粒子) / 解像度: 3.97 Å PDB-8ym4: Structure of Caspase-8/cFLIP death effector domain assembly 手法: X-RAY DIFFRACTION / 解像度: 2.34 Å PDB-8ym5: Structure of Caspase-8/cFLIP death effector domain assembly 手法: X-RAY DIFFRACTION / 解像度: 2.09 Å PDB-8ym6: Structure of Caspase-8/cFLIP death effector domain assembly 手法: X-RAY DIFFRACTION / 解像度: 3.3 Å
化合物	ChemComp-SE: SELENIUM ATOM / ヒドリドセレン ChemComp-HOH: WATER
由来	homo sapiens (ヒト)
キーワード	APOPTOSIS / FADD / Caspase-8 / cFLIP / death effector domain / cellular FLICE-like inhibitory protein