Dr. Alok K. Mitra
Department of Cell Biology
The Scripps Research Institute
La Jolla, CA

Tuesday, June 10, 1997
3:00 pm (CT)
3269 Beckman Institute

Abstract

Aquaporins (AQP) are members of the major intrinsic protein (MIP) superfamily of integral membrane proteins and facilitate transport of water in various eukaryotes and prokaryotes. The archetypal aquaporin AQP1 is a partially-glycosylated water-selective channel that is widely expressed in the plasma membranes of several water=D0permeable epithelial and endothelial cells. We report the three dimensional (3-D) structure of deglycosylated, human erythrocyte AQP1 determined at 7 A resolution in the membrane plane by electron crystallography of frozen-hydrated 2-D crystals. The structure displays a novel in-plane, intra-molecular 2-fold axis of symmetry located in the hydrophobic core of the bilayer. The AQP1 monomer is composed of six membrane-spanning, tilted a-helices. These helices form a barrel that encloses a vestibular region leading to the water-selective channel, which is outlined by densitites attributed to the functionally important NPA boxes and their bridges to the surrounding helices. The intra-molecular symmetry within the AQP1 molecule represents a novel motif for the topology and design of membrane protein channels and is a simple and elegant solution to the problem of bi-directional transport across the bilayer.

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