4c69

From Proteopedia

ATP binding to murine voltage-dependent anion channel 1 (mVDAC1).

Structural highlights

4c69 is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.277Å
Ligands:	ATP, LDA, MC3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VDAC1_MOUSE Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The voltage-dependent anion channel (VDAC) mediates the flow of metabolites and ions across the outer mitochondrial membrane of all eukaryotic cells. The open channel passes millions of ATP molecules per second, whereas the closed state exhibits no detectable ATP flux. High-resolution structures of VDAC1 revealed a 19-stranded beta-barrel with an alpha-helix partially occupying the central pore. To understand ATP permeation through VDAC, we solved the crystal structure of mouse VDAC1 (mVDAC1) in the presence of ATP, revealing a low-affinity binding site. Guided by these coordinates, we initiated hundreds of molecular dynamics simulations to construct a Markov state model of ATP permeation. These simulations indicate that ATP flows through VDAC through multiple pathways, in agreement with our structural data and experimentally determined physiological rates.

Structure-guided simulations illuminate the mechanism of ATP transport through VDAC1.,Choudhary OP, Paz A, Adelman JL, Colletier JP, Abramson J, Grabe M Nat Struct Mol Biol. 2014 Jun 8. doi: 10.1038/nsmb.2841. PMID:24908397^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations

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References

↑ Buettner R, Papoutsoglou G, Scemes E, Spray DC, Dermietzel R. Evidence for secretory pathway localization of a voltage-dependent anion channel isoform. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3201-6. PMID:10716730 doi:http://dx.doi.org/10.1073/pnas.060242297
↑ Okada SF, O'Neal WK, Huang P, Nicholas RA, Ostrowski LE, Craigen WJ, Lazarowski ER, Boucher RC. Voltage-dependent anion channel-1 (VDAC-1) contributes to ATP release and cell volume regulation in murine cells. J Gen Physiol. 2004 Nov;124(5):513-26. Epub 2004 Oct 11. PMID:15477379 doi:http://dx.doi.org/jgp.200409154
↑ Ujwal R, Cascio D, Colletier JP, Faham S, Zhang J, Toro L, Ping P, Abramson J. The crystal structure of mouse VDAC1 at 2.3 A resolution reveals mechanistic insights into metabolite gating. Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17742-7. Epub 2008 Nov 6. PMID:18988731 doi:0809634105
↑ Choudhary OP, Paz A, Adelman JL, Colletier JP, Abramson J, Grabe M. Structure-guided simulations illuminate the mechanism of ATP transport through VDAC1. Nat Struct Mol Biol. 2014 Jun 8. doi: 10.1038/nsmb.2841. PMID:24908397 doi:http://dx.doi.org/10.1038/nsmb.2841