8QNS

Crystal structure of murine AIF bound to N-terminal domain of CHCHD4

Summary for 8QNS

• Entry DOI: 10.2210/pdb8qns/pdb
• Descriptor: Apoptosis-inducing factor 1, mitochondrial, Mitochondrial intermembrane space import and assembly protein 40, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: apoptosis inducing factor, mitochondrial protein, fad, nad, protein complex, flavoprotein, rossmann fold topology, protein binding
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 8
• Total formula weight: 247045.33

Authors

Fagnani, E.,Milani, M. (deposition date: 2023-09-27, release date: 2024-05-08, Last modification date: 2024-11-20)

Primary citation

Fagnani, E.,Cocomazzi, P.,Pellegrino, S.,Tedeschi, G.,Scalvini, F.G.,Cossu, F.,Da Vela, S.,Aliverti, A.,Mastrangelo, E.,Milani, M.
CHCHD4 binding affects the active site of apoptosis inducing factor (AIF): Structural determinants for allosteric regulation.
Structure, 32:594-602.e4, 2024

PubMed Abstract: Apoptosis-inducing factor (AIF), which is confined to mitochondria of normal healthy cells, is the first identified caspase-independent cell death effector. Moreover, AIF is required for the optimal functioning of the respiratory chain machinery. Recent findings have revealed that AIF fulfills its pro-survival function by interacting with CHCHD4, a soluble mitochondrial protein which promotes the entrance and the oxidative folding of different proteins in the inner membrane space. Here, we report the crystal structure of the ternary complex involving the N-terminal 27-mer peptide of CHCHD4, NAD, and AIF harboring its FAD (flavin adenine dinucleotide) prosthetic group in oxidized form. Combining this information with biophysical and biochemical data on the CHCHD4/AIF complex, we provide a detailed structural description of the interaction between the two proteins, validated by both chemical cross-linking mass spectrometry analysis and site-directed mutagenesis.

PubMed: 38460521
DOI: 10.1016/j.str.2024.02.008

Experimental method

X-RAY DIFFRACTION (3.206 Å)