Hiller Sebastian, Wagner Gerhard
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Curr Opin Struct Biol. 2009 Aug;19(4):396-401. doi: 10.1016/j.sbi.2009.07.013. Epub 2009 Aug 7.
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.
电压依赖性阴离子通道（VDAC）是真核生物线粒体外膜中的一种重要蛋白质，为底物扩散提供通道。最近利用溶液核磁共振和X射线晶体学公布了VDAC同工型1在去污剂胶束和双分子层中的三种高分辨率结构。它们解决了关于VDAC膜拓扑结构的长期争论，并提供了首个真核生物β桶状膜蛋白结构。该结构包含一个此前在整合膜蛋白中未观察到的惊人特征：平行β链配对，因此是奇数条链。这些研究还为VDAC的电压门控机制及其受NADH调节提供了结构和功能基础；然而，它们尚未完全解释这些功能。随着VDAC - 1的从头结构以及其他六种蛋白质结构的出现，在过去两年中，通过溶液核磁共振解析的整合膜蛋白结构数量增加了一倍。对许多不同膜蛋白进行的大量进一步结构和功能研究表明，溶液核磁共振已成为膜蛋白分子生物学的重要工具。
