Structure of the voltage dependent anion channel: state of the art.
The eukaryotic porin or Voltage Dependent Anion-selective Channels (VDAC) is the protein forming the aqueous pore channel in the mitochondrial outer membrane. It can modulate the energy-dependent metabolism of the cell forming a diffusion barrier to ions, adenine-nucleotides and other metabolites and it is probably involved in the regulation of apoptotic-relevant events. For these reasons, VDAC co-responsibility in unphysiological events leading to important pathologies such as onset or sustainment of cancer has been envisaged very early. The knowledge of the VDAC atomic structure is thus a relevant step in the design of modern drugs acting upon the mitochondrial function and its related apoptotic balance. This goal, despite many efforts, has not been gained until now. Several predictive or descriptive techniques have been employed to obtain models or representations of the pore-structure. The results obtained are reported in this review. The emerging picture arising from these many results is coherent and sufficiently informative. From these efforts it appears that VDAC is functionally monomeric but can cluster in tight but regular groups; it is asymmetric with larger exposed domains on the cytosolic side of the outer mitochondrial membrane; the diameter of the pore is between 2.5-3.0 nm and it is apparently free from obstructions (in the open state); the channel wall is mainly formed by typical amphipathic beta-strands; mobile components (the N-terminal ?) can have functional relevance to the pore regulation.
De Pinto
Vito
V
Department of Chemical Sciences, University of Catania, Catania, Italy. vdpbiofa@mbox.unict.it
Reina
Simona
S
Guarino
Francesca
F
Messina
Angela
A
D000818:Animals; D017209:Apoptosis; D004734:Energy Metabolism; D006801:Humans; D017136:Ion Transport; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D050994:Voltage-Dependent Anion Channels / Q000737:chemistry / Q000378:metabolism*
D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D050994:Voltage-Dependent Anion Channels