Binding of chimeric analogs of omega-conotoxin MVIIA and MVIIC to the N- and P/Q-type calcium channels.
Despite their high sequence homology, the peptide neurotoxins omega-conotoxin MVIIA and MVIIC selectively block N- and P/Q-type calcium channels, respectively. To study the recognition mechanism of calcium channel subtypes, two chimeric analogs of omega-conotoxin MVIIA and MVIIC were synthesized by exchanging their N- and C-terminal halves. Binding assay for both N- and P/Q-type calcium channels showed that amino acid residues restricted to the N-terminal half are important for the recognition of N-type channels, whereas essential residues for P/Q-type channel recognition are widely spread over the whole omega-conotoxin molecule.
Sato
K
K
Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan. kazuki@libra.ls.m-kagaku.co.jp
Raymond
C
C
Martin-Moutot
N
N
Sasaki
T
T
Omori
A
A
Ohtake
A
A
Kim
J I
JI
Kohno
T
T
Takahashi
M
M
Seagar
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010446:Peptide Fragments; D010455:Peptides; D011993:Recombinant Fusion Proteins; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; C078452:ziconotide