architecture and selectivity in aquaporins 2.5 ？ x-ray structure of aquaporin z体系结构和选择性在水通道蛋白2.5 x射线结构水通道蛋白z.pdfVIP

PLoS BIOLOGY Architecture and Selectivity ˚ in Aquaporins 2.5: A X-Ray Structure of Aquaporin Z David F. Savage1,2, Pascal F. Egea1, Yaneth Robles-Colmenares 1, Joseph D. O’Connell III 1, Robert M. Stroud1* 1 Department of Biochemistry and Biophysics, University of California School of Medicine, San Francisco, California, United States of America, 2 Graduate Group in Biophysics, University of California, San Francisco, California, United States of America 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. Introduction