Recombinant Human VDAC1 protein

Voltage-Dependent Anion Channel 1 (VDAC1), a major pore-forming protein in the mitochondrial outer membrane, regulates the cross-membrane transport of metabolites, ions, and nucleotides, serving as a critical gateway for mitochondrial-nuclear communication. As the most abundant isoform of the VDAC family, it governs cellular energy metabolism by facilitating ATP/ADP exchange and modulating calcium signaling. Structurally, VDAC1 adopts a β-barrel conformation with 19 transmembrane β-strands and an N-terminal α-helix that dynamically regulates channel permeability. Its activity is modulated by post-translational modifications, including phosphorylation and acetylation, as well as interactions with apoptosis-related proteins like Bcl-2 family members.

Recombinant VDAC1 protein, typically expressed in bacterial (E. coli) or eukaryotic systems, enables structural and functional studies of this channel protein. Purification strategies often incorporate affinity tags (e.g., His-tag) followed by ion-exchange chromatography. The recombinant form has been instrumental in resolving VDAC1's 3D structure through NMR and X-ray crystallography, revealing voltage-gating mechanisms and interaction sites for metabolic enzymes like hexokinase.

Research highlights VDAC1's dual role in cell survival and death: it maintains metabolic homeostasis under normal conditions but participates in apoptotic signaling through cytochrome c release during stress. Dysregulation of VDAC1 is implicated in cancer (metabolic reprogramming), neurodegenerative diseases (mitochondrial dysfunction), and cardiovascular disorders. Recent studies explore its potential as a therapeutic target, with recombinant VDAC1 serving as a platform for screening channel modulators and investigating pathological protein interactions (e.g., amyloid-β in Alzheimer's). Current challenges in recombinant applications include maintaining native conformation and resolving oligomerization effects on channel properties.