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==Magic-angle spinning NMR structure of the human voltage-dependent anion channel 1 (E73V/C127A/C232S) in DMPC lipid bilayers==
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== Structural highlights ==
<table><tr><td colspan='2'>Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QI2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solid-state NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qi2 OCA], [https://pdbe.org/7qi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qi2 RCSB], [https://www.ebi.ac.uk/pdbsum/7qi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qi2 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The voltage-dependent anion channel (VDAC), the most abundant protein in the outer mitochondrial membrane, is responsible for the transport of all ions and metabolites into and out of mitochondria. Larger than any of the beta-barrel structures determined to date by magic-angle spinning (MAS) NMR, but smaller than the size limit of cryo-electron microscopy (cryo-EM), VDAC1's 31 kDa size has long been a bottleneck in determining its structure in a near-native lipid bilayer environment. Using a single two-dimensional (2D) crystalline sample of human VDAC1 in lipids, we applied proton-detected fast magic-angle spinning NMR spectroscopy to determine the arrangement of beta strands. Combining these data with long-range restraints from a spin-labeled sample, chemical shift-based secondary structure prediction, and previous MAS NMR and atomic force microscopy (AFM) data, we determined the channel's structure at a 2.2 A root-mean-square deviation (RMSD). The structure, a 19-stranded beta-barrel, with an N-terminal alpha-helix in the pore is in agreement with previous data in detergent, which was questioned due to the potential for the detergent to perturb the protein's functional structure. Using a quintuple mutant implementing the channel's closed state, we found that dynamics are a key element in the protein's gating behavior, as channel closure leads to the destabilization of not only the C-terminal barrel residues but also the alpha2 helix. We showed that cholesterol, previously shown to reduce the frequency of channel closure, stabilizes the barrel relative to the N-terminal helix. Furthermore, we observed channel closure through steric blockage by a drug shown to selectively bind to the channel, the Bcl2-antisense oligonucleotide G3139.

Structure and Gating Behavior of the Human Integral Membrane Protein VDAC1 in a Lipid Bilayer.,Najbauer EE, Tekwani Movellan K, Giller K, Benz R, Becker S, Griesinger C, Andreas LB J Am Chem Soc. 2022 Feb 23;144(7):2953-2967. doi: 10.1021/jacs.1c09848. Epub 2022, Feb 14. PMID:35164499<ref>PMID:35164499</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
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[[Category: Large Structures]]
[[Category: Andreas LB]]
[[Category: Najbauer EE]]