Book of Abstracts: Albany 2007
June 19-23 2007
Structure and function of channels
A biological cell, such as a nerve cell, regulates cell signalling mainly by ion channels. Water permeation through biomembranes should therefore be strictly separated from the movement of ions This means water channels must be highly specific and effective for water to prevent any ions. One water channel can permeate 2 billion water molecules in a second without proton permeation. When water molecules rapidly cross the membrane channel, they form a continuous unbroken column and their hydrogen-bond chain conducts protons with great efficiency. The pore has to prevent proton passage and the hydrogen-bond separation is required while such requirement increases energy barrier reducing the water permeation speed. For answering these questions, structure of aquaporin-1 was analysed at a resolution of 3.8 Å by electron crystallography . For accomplishing the effective water channel functions, the structure showed peculiar structural determinants including an unusual fold, for which we named aquaporin fold . Based on the structure of aquaporin-1, we proposed H-bond isolation mechanism by which we could explain a mechanism of high speed water permeation without transfer of protons. However, the resolution was limited and we could observe no water molecules in the structure analysis of aquaporin-1. After finding of aquaporin-1, thirteen water channels, aquaporin-0 to 12, were identified in human body. By analyzing structure of aquaporin-0 at a resolution of 1.9 Å, we could confirm the H-bond isolation mechanism .
Fig.1 Double layered structure of aquaporin-4 analysed by electron crystallography
Aquaporin-4 is the predominant water channel in brain and is abundantly expressed in glial cells, particularly in glial end feet where it forms orthogonal arrays and in glial lamellae of the hypothalamus. Two-dimensional crystals, showing the same molecular packing as the orthogonal arrays in vivo, were analysed to 3.2 Å resolution . The analysed structure reveals weak but specific interactions between interacting tetramers in adjoining membranes, suggesting a structural role for aquaporine-4 in the adhesion of membrane layers in glial lamellae as shown in Fig.1. The aquaporin-4 molecule acquired two very important functions in cell biology, cell adhesive and channel functions. We named and would like to call this type channels as ?Adhennel? family . We recently analysed structure of an Adhennel family protein, Gap Junction channel. Based on the structure of the channel: Cx26, we would like to propose a plug gating model . We also analysed structures of channels, voltage sensitive Na+-channel  and IP3 receptor  by single particle method, while the resolutions are limited. By focusing on multifunctional channels, I would like to introduce recent results in structural biology of membrane proteins by utilizing our cryo-electron microscope with helium cooled specimen stage .
References and Footnotes
Department of Biophysics,