3GD4

Crystal structure of the reduced, NAD-bound form of murine apoptosis inducing factor

3GD4 の概要

• エントリーDOI: 10.2210/pdb3gd4/pdb
• 関連するPDBエントリー: 1GV4 1M6I 3GD3
• 分子名称: Apoptosis-inducing factor 1, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: alpha-beta protein, acetylation, apoptosis, dna-binding, fad, flavoprotein, mitochondrion, nucleus, oxidoreductase, phosphoprotein, transit peptide
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Mitochondrion intermembrane space: Q9Z0X1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114056.07

構造登録者

Sevrioukova, I.F. (登録日: 2009-02-23, 公開日: 2009-05-19, 最終更新日: 2023-09-06)

主引用文献

Sevrioukova, I.F.
Redox-linked conformational dynamics in apoptosis-inducing factor
J.Mol.Biol., 390:924-938, 2009

PubMed Abstract: Apoptosis-inducing factor (AIF) is a bifunctional mitochondrial flavoprotein critical for energy metabolism and induction of caspase-independent apoptosis, whose exact role in normal mitochondria remains unknown. Upon reduction with NADH, AIF undergoes dimerization and forms tight, long-lived FADH(2)-NAD charge-transfer complexes (CTC) that are proposed to be functionally important. To obtain a deeper insight into structure/function relations and redox mechanism of this vitally important protein, we determined the X-ray structures of oxidized and NADH-reduced forms of naturally folded recombinant murine AIF. Our structures reveal that CTC with the pyridine nucleotide is stabilized by (i) pi-stacking interactions between coplanar nicotinamide, isoalloxazine, and Phe309 rings; (ii) rearrangement of multiple aromatic residues in the C-terminal domain, likely serving as an electron delocalization site; and (iii) an extensive hydrogen-bonding network involving His453, a key residue that undergoes a conformational switch to directly interact with and optimally orient the nicotinamide for charge transfer. Via the His453-containing peptide, redox changes in the active site are transmitted to the surface, promoting AIF dimerization and restricting access to a primary nuclear localization signal through which the apoptogenic form is transported to the nucleus. Structural findings agree with biochemical data and support the hypothesis that both normal and apoptogenic functions of AIF are controlled by NADH.

PubMed: 19447115
DOI: 10.1016/j.jmb.2009.05.013

実験手法

X-RAY DIFFRACTION (2.24 Å)