Latent specificity of molecular recognition in sodium channels engineered to discriminate between two "indistinguishable" mu-conotoxins.
Biochemistry
; 40(20): 6002-8, 2001 May 22.
Article
em En
| MEDLINE
| ID: mdl-11352735
ABSTRACT
mu-Conotoxins (mu-CTX) are potent oligopeptide blockers of sodium channels. The best characterized forms of mu-CTX, GIIIA and GIIIB, have similar primary and three-dimensional structures and comparable potencies (IC(50) approximately 30 nM) for block of wild-type skeletal muscle Na(+) channels. The two toxins are thus considered to be indistinguishable by their target channels. We have found mutations in the domain II pore region (D762K and E765K) that decrease GIIIB blocking affinity approximately 200-fold, but reduce GIIIA affinity by only approximately 4-fold, compared with wild-type channels. Synthetic mu-CTX GIIIA mutants reveal that the critical residue for differential recognition is at position 14, the site of the only charge difference between the two toxin isoforms. Therefore, engineered Na(+) channels, but not wild-type channels, can discriminate between two highly homologous conotoxins. Latent specificity of toxin-channel interactions, such as that revealed here, is a principle worthy of exploitation in the design and construction of improved biosensors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Sódio
/
Mutagênese Sítio-Dirigida
/
Conotoxinas
/
Bloqueadores dos Canais de Sódio
/
Venenos de Moluscos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos