3SHF

Crystal structure of the R265S mutant of full-length murine Apaf-1

Summary for 3SHF

• Entry DOI: 10.2210/pdb3shf/pdb
• Related: 3sfz
• Descriptor: Apoptotic peptidase activating factor 1, ADENOSINE-5'-DIPHOSPHATE, GAMMA-BUTYROLACTONE, ... (4 entities in total)
• Functional Keywords: tandem beta-propeller, apoptosis, cytochrome c, adenine nucleotide, procaspase-9, cytosol
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 1
• Total formula weight: 142458.61

Authors

Eschenburg, S.,Reubold, T.F. (deposition date: 2011-06-16, release date: 2011-08-24, Last modification date: 2024-11-06)

Primary citation

Reubold, T.F.,Wohlgemuth, S.,Eschenburg, S.
Crystal structure of full-length Apaf-1: how the death signal is relayed in the mitochondrial pathway of apoptosis.
Structure, 19:1074-1083, 2011

PubMed Abstract: 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 Å 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 Å resolution and we show that proper function of Apaf-1 relies on R265 in the vicinity of the bound nucleotide.

PubMed: 21827944
DOI: 10.1016/j.str.2011.05.013

Experimental method

X-RAY DIFFRACTION (3.55 Å)