Savage David F, Egea Pascal F, Robles-Colmenares Yaneth, O'Connell Joseph D, Stroud Robert M
Department of Biochemistry and Biophysics, University of California School of Medicine, San Francisco, California, USA.
PLoS Biol. 2003 Dec;1(3):E72. doi: 10.1371/journal.pbio.0000072. Epub 2003 Dec 22.
Aquaporins are a family of water and small molecule channels found in organisms ranging from bacteria to animals. One of these channels, the E. coli protein aquaporin Z (AqpZ), has been shown to selectively conduct only water at high rates. We have expressed, purified, crystallized, and solved the X-ray structure of AqpZ. The 2.5 A resolution structure of AqpZ suggests aquaporin selectivity results both from a steric mechanism due to pore size and from specific amino acid substitutions that regulate the preference for a hydrophobic or hydrophilic substrate. This structure provides direct evidence on the molecular mechanisms of specificity between water and glycerol in this family of channels from a single species. It is to our knowledge the first atomic resolution structure of a recombinant aquaporin and so provides a platform for combined genetic, mutational, functional, and structural determinations of the mechanisms of aquaporins and, more generally, the assembly of multimeric membrane proteins.
水通道蛋白是一类存在于从细菌到动物等多种生物体中的水和小分子通道。其中一种通道，即大肠杆菌蛋白水通道蛋白Z（AqpZ），已被证明仅能高效选择性地传导水。我们对AqpZ进行了表达、纯化、结晶并解析了其X射线结构。AqpZ分辨率为2.5埃的结构表明，水通道蛋白的选择性既源于孔径导致的空间机制，也源于特定氨基酸取代，这些取代调节了对疏水或亲水底物的偏好。该结构为单一物种的这一通道家族中水与甘油之间特异性的分子机制提供了直接证据。据我们所知，这是重组水通道蛋白的首个原子分辨率结构，因此为水通道蛋白机制以及更广泛的多聚体膜蛋白组装的联合遗传、突变、功能和结构测定提供了一个平台。
