STRUCTURAL MODELS OF THE TRANSMEMBRANE REGION OF VOLTAGE-GATED AND OTHER K+ CHANNELS IN OPEN, CLOSED, AND INACTIVATED CONFORMATIONS

Citation
Sr. Durell et al., STRUCTURAL MODELS OF THE TRANSMEMBRANE REGION OF VOLTAGE-GATED AND OTHER K+ CHANNELS IN OPEN, CLOSED, AND INACTIVATED CONFORMATIONS, Journal of structural biology, 121(2), 1998, pp. 263-284
Citations number
91
Categorie Soggetti
Biophysics,Biology,"Cell Biology
ISSN journal
10478477
Volume
121
Issue
2
Year of publication
1998
Pages
263 - 284
Database
ISI
SICI code
1047-8477(1998)121:2<263:SMOTTR>2.0.ZU;2-9
Abstract
A large collaborative, multidisciplinary effort involving many researc h laboratories continues which uses indirect methods of molecular biol ogy and membrane biophysics to analyze the three-dimensional structure s and functional mechanisms of K+ channels. This work also extends to the distant relatives of these channels, including the voltage-gated N a+ and Ca2+ channels. The role that our group plays in this process is to combine the information gained from experimental studies with mole cular modeling techniques to generate atomic-scale structural models o f these proteins. The modeling process involves three stages which are summarized as: (I) prediction of the channel sequence transmembrane t opology, including the functionality and secondary structure of the se gments; (II) prediction of the relative positions of the transmembrane segments, and (III) filling in all atoms of the amino acid residues, with conformations for energetically stabilized interactions. Both phy siochemical and evolutionary principles (including sequence homology a nalysis) are used to guide the development. In addition to testing the steric and energetic feasibilities of different structural hypotheses , the models provide guidance for the design of new experiments. Struc tural modeling also serves to ''fill in the gaps'' of experimental dat a, such as predicting additional residue interactions and conformation al changes responsible for functional processes. The modeling process is currently at the stage that experimental studies have definitely co nfirmed most of our earlier predictions about the transmembrane topolo gy and functionality of different segments. Additionally, this report describes the detailed, three-dimensional models we have developed for the entire transmembrane region and important functional sites of the voltage-gated Shaker K+ channel in the open, closed, and inactivated conformations (including the ion-selective pore and voltage-sensor reg ions). As part of this effort, we also describe how our development of structural models for many of the other major K+ channel families aid s in determining common structural motifs. As an example, we also pres ent a detailed model of the smaller, bacterial K+ channel from Strepto myces lividans. Finally, we discuss strategies for using newly develop ed experimental methods for determining the structures and analyzing t he functions of these channel proteins. (C) 1998 Academic Press.