Professor Alok Mitra
The Scripps Research Institute
La Jolla, CA

Thursday, April 16, 1998
3:00 pm (CT)
3269 Beckman Institute

Abstract

The three-dimensional structure of aquaporin 1(AQP1) water channel in the lipid-bilayer was determined at 7† resolution by electron cryo-crystallography. The crystallographic data, consisting of phases extracted directly from images and amplitudes calculated from electron-diffraction patterns, were generated from tilted views of frozen-hydrated (-176oC) 2-C crystals of AQP1. The calculated 3-D density map led to the visualization of the unperturbed structure of AQP1 in the lipid bilayer. The structure has a novel in-plane, intramolecular 2-fold axis of symmetry located in the hydrophobic core of the molecule. The AQP1 monomer is composed of six membrane-spanning, tilted a-helices that form a right-handed barrel. The helix barrel encloses a vestibular region leading to the water-selective channel which is outlined by densities attributed to hydrophobic loops containing the absolutely conserved NPA triplets in the homologous N-and C-terminal halves of the polypeptide chain. The intramolecular symmetry within the AQP1 moleculare represents a new motif for the topology and design of membrane protein channels, and is a simple and elegant solution to the problem of unidirectional transport across the bilayer.

Tea and coffee will be served in R3151 Beckman Institute at 2:15pm.