Abstract
omega-Conotoxin MVIIC binds to P/Q-type calcium channels with high affinity and N-type channels with low affinity. To reveal the residues essential for subtype selectivity, we synthesized Ala-scanning analogs of MVIIC. Binding assays using rat cerebellar P(2) membranes suggested that Thr(11), Tyr(13) and Lys(2) are essential for binding to both N- and P/Q-type channels, whereas Lys(4) and Arg(22) are important for binding to P/Q-type channels. These results suggest that MVIIC interacts with P/Q-type channels via a large surface, in good agreement with previous observations using chimeric analogs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine / chemistry*
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Amino Acid Sequence
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Animals
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Calcium Channel Blockers / chemical synthesis
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Calcium Channel Blockers / chemistry
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Calcium Channel Blockers / metabolism*
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Calcium Channels, N-Type / metabolism*
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Calcium Channels, P-Type / metabolism*
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Calcium Channels, Q-Type / metabolism*
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Cerebellum / metabolism
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Chromatography, High Pressure Liquid
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Circular Dichroism
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Disulfides / chemistry
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In Vitro Techniques
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Intracellular Membranes / physiology
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Ion Channel Gating
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Models, Molecular
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Molecular Sequence Data
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Protein Binding
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Rats
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Structure-Activity Relationship
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omega-Conotoxins / chemical synthesis
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omega-Conotoxins / chemistry
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omega-Conotoxins / metabolism*
Substances
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Calcium Channel Blockers
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Calcium Channels, N-Type
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Calcium Channels, P-Type
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Calcium Channels, Q-Type
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Disulfides
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omega-Conotoxins
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omega-conotoxin-MVIIC
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Alanine