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Channel Proteins: From Anatomy to Design

  • Conference paper
Membrane Proteins: Structures, Interactions and Models

Part of the book series: The Jerusalem Symposia on Quantum Chemistry and Biochemistry ((JSQC,volume 25))

Abstract

The precise mechanisms of action of channel proteins have not been delineated; accordingly, we aim to identify principles that define the biological design of channel proteins, to realize the molecular design of a pore forming structure, and to use it towards understanding the molecular basis of ionic selectivity and channel blockade. As a first step towards the design of channel proteins, we set out to model only the inner pore-forming element. This endeavor has suggested a molecular blueprint for the pore-forming structure of channel proteins: a bundle of amphipathic a-helices that cluster together to generate a central hydrophilic channel. The pore-forming structures are engineered from functional modules that represent the amino acid sequence of authentic proteins and refined to accommodate specific functional characteristics. The strength of the strategy is that the design can be realized and the validity of the proposed structural motif evaluated experimentally. Accordingly, four-helix bundle proteins that span the lipid bilayer and provide binding sites for permeant ions and for specific channel modulators have been generated; these synthetic channel proteins mimic properties of corresponding authentic proteins. Since high resolution structural information is not yet available, the uniqueness and significance of this approach is evident: the ability to produce proteins with predicted functional attributes by emulating the authentic sequences affords, for the first time, clues to the biological design of channel proteins. The emergence of the structure model integrated with the benefits of chemical synthesis provides, a means to evaluate sites of action for channel modifiers and may facilitate the conceptual design of channel blocking drugs.

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Author information

Authors and Affiliations

  1. Department of Biology, University of California San Diego, La Jolla, CA, 92093-0319

    Anne Grove, Myrta S. Montal, G. Laxma Reddy & Stephan Marrer

  2. Departments of Pediatrics and Biochemistry, University of Southern California Medical School and Childrens Hospital Los Angeles, Los Angeles, CA, 90054-0700

    Takeo Iwamoto, John Tomich & Mauricio Montal

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  1. Anne Grove
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  2. Myrta S. Montal
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  3. G. Laxma Reddy
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  4. Stephan Marrer
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  5. Takeo Iwamoto
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  6. John Tomich
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  7. Mauricio Montal
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Editors and Affiliations

  1. Institut de Biologie Physico-Chimique, Fondation Edmond de Rothschild, Paris, France

    Alberte Pullman  & Bernard Pullman  & 

  2. Department of Chemistry, University of Tel-Aviv, Israel

    Joshua Jortner

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Grove, A. et al. (1992). Channel Proteins: From Anatomy to Design. In: Pullman, A., Jortner, J., Pullman, B. (eds) Membrane Proteins: Structures, Interactions and Models. The Jerusalem Symposia on Quantum Chemistry and Biochemistry, vol 25. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-2718-9_22

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  • DOI: https://doi.org/10.1007/978-94-011-2718-9_22

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