scholarly journals ATP Flux Is Controlled by a Voltage-gated Channel from the Mitochondrial Outer Membrane

1996 ◽  
Vol 271 (45) ◽  
pp. 28006-28008 ◽  
Author(s):  
Tatiana Rostovtseva ◽  
Marco Colombini
Keyword(s):  
Outer Membrane ◽  
Mitochondrial Outer Membrane ◽  
Voltage Gated ◽  
Gated Channel

Structure of crystalline VDAC, the voltage-gated channel in the mitochondrial outer membrane

1992 ◽  
Vol 50 (1) ◽  
pp. 440-441
Author(s):  
X.W. Guo ◽  
P.R. Smith ◽  
M. Radermacher ◽  
C.A. Mannella
Keyword(s):  
Neurospora Crassa ◽  
Outer Membrane ◽  
Repeat Unit ◽  
Mitochondrial Outer Membrane ◽  
Lattice Contraction ◽  
Outer Membranes ◽  
Voltage Gated ◽  
Lateral Contraction ◽  
Gated Channel ◽  
Projection Images

The voltage-gated, mitochondrial channel, VDAC, is formed by a 31-kDa outer-membrane polypeptide. Crystalline arrays of this channel, produced by phospholipase A2 treatment of Neurospora crassa mitochondrial outer membranes, consist of groups of 6 channels repeated on a parallelogram (“oblique”) lattice (a=13.3nm, b=11.5nm, γ = 109°). These membrane crystals are polymorphic, i.e. lateral contraction is triggered by a polyanion which also decreases VDAC’s gating potential. Projection images of unstained, frozen-hydrated VDAC arrays indicate that lattice contraction is accompanied by changes in the distribution of protein away from the hexameric repeat unit.

Identification of the mutated sites present in the transmembrane regions of SCN1A_HUMAN (Sodium Voltage-Gated Channel Alpha Subunit 1) using Insilico techniques

2020 ◽  
Vol 5 (1) ◽  
pp. 1-6
Author(s):  
Balaji Munivelan
Keyword(s):  
Amino Acids ◽  
Outer Membrane ◽  
Structure Prediction ◽  
Homology Modelling ◽  
Transmembrane Helix ◽  
3D Structure ◽  
Docking Studies ◽  
Alpha Subunit ◽  
Voltage Gated ◽  
Gated Channel

Mutations in numerous genes which encode for voltage-gated sodium channels give rise to various epilepsy syndromes in humans. Our research investigation mainly focuses on the identification of the integral membrane protein of the SCN1A (Sodium Voltage-Gated Channel Alpha Subunit 1) in humans. Secondary, we focus on the transmembrane membrane (TP) amino acids directly involved in the epilepsy-involved mutated regions. Using Insilico protocols, we identify the TP proteins and amino acids and elucidate the Transmembrane Helix and the inside and outside amino acids regions of the SCN1A. With the help of Insilico proteomics server, the amino acids in the mutated regions involved in the TP were identified. Finally, 3D structure prediction was performed using homology modelling server and the modelled structure was cross validated for the TP and validated. The identified results were validated using molecular visualization tools. We prove that the mutated amino acids are present in the outer membrane of the TP regions. Thus, the outer membrane of sodium channel and the amino acids present in the outer membrane (T875M, R859C, and R1648H) play a vital role in Structure-Based Drug Designing and Drug Docking studies.

Cryo-Electron Microscopy and Correlation Averaging of Frozen-Hydrated, Polymorphic 2D Crystals of the Mitochondrial Outer Membrane Channel

1990 ◽  
Vol 48 (1) ◽  
pp. 100-101
Author(s):  
Xiao-Wei Guo
Keyword(s):  
Outer Membrane ◽  
Hexagonal Lattice ◽  
Mitochondrial Outer Membrane ◽  
Rectangular Lattice ◽  
Electron Microscopic ◽  
Cryo Electron Microscopy ◽  
Voltage Dependent ◽  
Outer Membrane Channel ◽  
2D Crystals ◽  
Vdac Channel

Voltage-dependent, anion-selective channels (VDAC) are formed in the mitochondrial outer membrane (mitOM) by a 30-kDa polypeptide. These channels form ordered 2D arrays when mitOMs from Neurospora crassa are treated with soluble phospholipase A2. We obtain low-dose electron microscopic images of unstained specimens of VDAC crystals preserved in vitreous ice, using a Philips EM420 equipped with a Gatan cryo-transfer stage. We then use correlation analysis to compute average projections of the channel crystals. The procedure involves Fourier-filtration of a region within a crystal field to obtain a preliminary average that is subsequently cross-correlated with the entire crystal. Subregions are windowed from the crystal image at coordinates of peaks in the cross-correlation function (CCF, see Figures 1 and 2) and summed to form averages (Figure 3).The VDAC channel forms several different types of crystalline arrays in mitOMs. The polymorph first observed during phospholipase treatment is a parallelogram array (a=13 run, b=11.5 run, θ==109°) containing 6 water-filled pores per unit cell. Figure 1 shows the CCF of a sub-field of such an “oblique” array used to compute the correlation average of Figure 3A. With increased phospholipase treatment, other polymorphs are observed, often co-existing within the same crystal. For example, two distinct (but closely related) types of lattices occur in the field corresponding to the CCF of Figure 2: a “contracted” version of the parallelogram lattice (a=13 run, b=10 run, θ=99°), and a near-rectangular lattice (a=8.5 run, b=5 nm). The pattern of maxima in this CCF suggests that a third, near-hexagonal lattice (a=4.5 nm) may also be present. The correlation averages of Figures 3B-D were computed from polycrystalline fields, using peak coordinates in regions of CCFs corresponding to each of the three lattice types.

Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC

2004 ◽  
Vol 286 (5) ◽  
pp. C1109-C1117 ◽  
Author(s):  
Liang Guo ◽  
Dawn Pietkiewicz ◽  
Evgeny V. Pavlov ◽  
Sergey M. Grigoriev ◽  
John J. Kasianowicz ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Outer Membrane ◽  
Cell Types ◽  
Rnase A ◽  
Mitochondrial Outer Membrane ◽  
Dependent Manner ◽  
Mitochondrial Apoptosis ◽  
Noise Type ◽  
Voltage Dependent

Recent studies indicate that cytochrome c is released early in apoptosis without loss of integrity of the mitochondrial outer membrane in some cell types. The high-conductance mitochondrial apoptosis-induced channel (MAC) forms in the outer membrane early in apoptosis of FL5.12 cells. Physiological (micromolar) levels of cytochrome c alter MAC activity, and these effects are referred to as types 1 and 2. Type 1 effects are consistent with a partitioning of cytochrome c into the pore of MAC and include a modest decrease in conductance that is dose and voltage dependent, reversible, and has an increase in noise. Type 2 effects may correspond to “plugging” of the pore or destabilization of the open state. Type 2 effects are a dose-dependent, voltage-independent, and irreversible decrease in conductance. MAC is a heterogeneous channel with variable conductance. Cytochrome c affects MAC in a pore size-dependent manner, with maximal effects of cytochrome c on MAC with conductance of 1.9–5.4 nS. The effects of cytochrome c, RNase A, and high salt on MAC indicate that size, rather than charge, is crucial. The effects of dextran molecules of various sizes indicate that the pore diameter of MAC is slightly larger than that of 17-kDa dextran, which should be sufficient to allow the passage of 12-kDa cytochrome c. These findings are consistent with the notion that MAC is the pore through which cytochrome c is released from mitochondria during apoptosis.

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