Research Article: Architecture and Selectivity in Aquaporins: 2.5 Å X-Ray Structure of Aquaporin Z

Date Published: December 22, 2003

Publisher: Public Library of Science

Author(s): David F Savage, Pascal F Egea, Yaneth Robles-Colmenares, Joseph D. O’Connell III, Robert M Stroud

Abstract: 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 Å 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.

Partial Text: The aquaporin family, composed of transmembrane water-conducting channels (aquaporins) and glycerol (and water)-conducting channels (aquaglyceroporins), is a group of highly selective passive transporters (Heller et al. 1980; Preston et al. 1992; Park and Saier 1996). The diversity of the aquaporin family is embodied by the human proteome, where at least ten different aquaporins are expressed in tissues and cells such as brain, kidneys, and erythrocytes. Aquaporins play a fundamental role in osmoregulation, and mutations are responsible for human diseases ranging from diabetes insipidus to congenital cataract formation (Borgnia et al. 1999b).

The aquaporin channel is a long (approximately 28 Å) and narrow (less than 4 Å diameter) pore that widens out to periplasmic and cytoplasmic vestibules. The channel is formed by the packing of helices M1–M3 and M5–M7 and is amphipathic, establishing a single-file water conduction pathway. The hydrophilic nature of the channel results from the four adjacent carbonyls of G59 (GlpF number 64), G60(65), H61(66), and F62(67) from the amino-terminal domain and the quasi-2-fold related N182(199), T183(200), S184(201), and V185(202) from the carboxy-terminal domain (Figure 1B). The hydrophobic nature of the channel results from an abundance of valines, phenylalanines, and isoleucines within the channel.

Source:

http://doi.org/10.1371/journal.pbio.0000072

 

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