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-Structure paper
タイトル | A near atomic structure of the active human apoptosome. |
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ジャーナル・号・ページ | Elife, Vol. 5, Year 2016 |
掲載日 | 2016年10月4日 |
著者 | Tat Cheung Cheng / Chuan Hong / Ildikó V Akey / Shujun Yuan / Christopher W Akey / |
PubMed 要旨 | In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo- ...In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease. |
リンク | Elife / PubMed:27697150 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.1 Å |
構造データ | |
化合物 | ChemComp-DTP: ChemComp-HEC: |
由来 |
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キーワード | APOPTOSIS / Apaf-1 / programmed cell death / AAA+ ATPase |