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10.1038/ncomms13565

http://scihub22266oqcxt.onion/10.1038/ncomms13565
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C5123071!5123071!27882936
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suck abstract from ncbi


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pmid27882936      Nat+Commun 2016 ; 7 (ä): ä
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  • The Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with distinct activities #MMPMID27882936
  • Wu CC; Lee S; Malladi S; Chen MD; Mastrandrea NJ; Zhang Z; Bratton SB
  • Nat Commun 2016[]; 7 (ä): ä PMID27882936show ga
  • According to dogma, initiator caspases are activated through proximity-induced homodimerization, but some studies infer that during apoptosis caspase-9 may instead form a holoenzyme with the Apaf-1 apoptosome. Using several biochemical approaches, including a novel site-specific crosslinking technique, we provide the first direct evidence that procaspase-9 homodimerizes within the apoptosome, markedly increasing its avidity for the complex and inducing selective intramolecular cleavage at Asp-315. Remarkably, however, procaspase-9 could also bind via its small subunit to the NOD domain in Apaf-1, resulting in the formation of a heterodimer that more efficiently activated procaspase-3. Following cleavage, the intersubunit linker (and associated conformational changes) in caspase-9-p35/p12 inhibited its ability to form homo- and heterodimers, but feedback cleavage by caspase-3 at Asp-330 removed the linker entirely and partially restored activity to caspase-9-p35/p10. Thus, the apoptosome mediates the formation of caspase-9 homo- and heterodimers, both of which are impacted by cleavage and contribute to its overall function.
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