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Publication Abstract from PubMed

The apoptotic protease-activating factor 1 (Apaf-1) relays the death signal in the mitochondrial pathway of apoptosis. Apaf-1 oligomerizes on binding of mitochondrially released cytochrome c into the heptameric apoptosome complex to ignite the downstream cascade of caspases. Here, we present the 3.0 A crystal structure of full-length murine Apaf-1 in the absence of cytochrome c. The structure shows how the mammalian death switch is kept in its "off" position. By comparing the off state with a recent cryo-electron microscopy derived model of Apaf-1 in its apoptosomal conformation, we depict the molecular events that transform Apaf-1 from autoinhibited monomer to a building block of the caspase-activating apoptosome. Moreover, we have solved the crystal structure of the R265S mutant of full-length murine Apaf-1 in the absence of cytochrome c to 3.55 A resolution and we show that proper function of Apaf-1 relies on R265 in the vicinity of the bound nucleotide.

Crystal structure of full-length apaf-1: how the death signal is relayed in the mitochondrial pathway of apoptosis.,Reubold TF, Wohlgemuth S, Eschenburg S Structure. 2011 Aug 10;19(8):1074-83. PMID:21827944^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.