Article

The role of solution NMR in the structure determinations of VDAC-1 and other membrane proteins.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Current Opinion in Structural Biology (Impact Factor: 8.75). 09/2009; 19(4):396-401. DOI: 10.1016/j.sbi.2009.07.013
Source: PubMed

ABSTRACT The voltage-dependent anion channel (VDAC) is an essential protein in the eukaryotic outer mitochondrial membrane, providing the pore for substrate diffusion. Three high-resolution structures of the isoform 1 of VDAC in detergent micelles and bicelles have recently been published, using solution NMR and X-ray crystallography. They resolve longstanding discussions about the membrane topology of VDAC and provide the first eukaryotic beta-barrel membrane protein structure. The structure contains a surprising feature that had not been observed in an integral membrane protein before: A parallel beta-strand pairing and thus an odd number of strands. The studies also give a structural and functional basis for the voltage gating mechanism of VDAC and its modulation by NADH; however, they do not fully explain these functions yet. With the de novo structure of VDAC-1, as well as those of half a dozen other proteins, the number of integral membrane protein structures solved by solution NMR has doubled in the past two years. Numerous further structural and functional studies on many different membrane proteins show that solution NMR has become an important tool for membrane protein molecular biology.

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