title: Structural clues in the sequences of the aquaporins.
abstract: The large number of sequences available for the aquaporin family represents a valuable source of information to incorporate into three-dimensional structure determination. Phylogenetic analysis was used to define type sequences to avoid extreme over-representation of some subfamilies, and as a measure of the quality of multiple sequence alignment. Inspection of the sequence alignment suggested eight conserved segments that define the core architecture of six transmembrane helices and two functional loops, B and E, projecting into the plane of the membrane. The sum of the core segments and the minimum lengths of the interlinking loops constitute the 208 residues necessary to satisfy the aquaporin architecture. Analysis of hydrophobic and conservation periodicity and of correlated mutations across the alignment indicated the likely assignment and orientation of the helices in the bilayer. This assignment is examined with respect to the structure of the erythrocyte aquaporin 1 determined by electron crystallography. The aquaporin 1 tetramer is described as three rings of helices, each ring with a different exposure to the lipid environment. The sequence analysis clearly suggests that two helices are exposed along their whole lengths, two helices are exposed only at their N termini, and two helices are not exposed to lipid. It is further proposed that, besides loops B and E, the highly conserved motifs on helices 1 and 4, ExxxTxxF/L, could line the water channel.
authors.affiliation: M. E. Müller Institute for Microscopic Structural Biology, Biozentrum, CH-4056, Switzerland. heymann@ubaclu.unibas.ch
authors.forename: J B
authors.initials: JB
authors.lastname: Heymann
authors.forename: A
authors.initials: A
authors.lastname: Engel
mesh_terms: D000595:Amino Acid Sequence; D051398:Aquaporin 1; D020346:Aquaporins / Q000737:chemistry*; D001789:Blood Group Antigens; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: C496020:AQP1 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D046911:Macromolecular Substances; D051398:Aquaporin 1