Structure-activity relationships of ω-Agatoxin IVA in lipid membranes.
Biochem Biophys Res Commun
; 482(1): 170-175, 2017 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-27838299
ABSTRACT
To analyze structural features of ω-Aga IVA, a gating modifier toxin from spider venom, we here investigated the NMR solution structure of ω-Aga IVA within DPC micelles. Under those conditions, the Cys-rich central region of ω-Aga IVA still retains the inhibitor Cys knot motif with three short antiparallel ß-strands seen in water. However, 15N HSQC spectra of ω-Aga IVA within micelles revealed that there are radical changes to the toxin's C-terminal tail and several loops upon binding to micelles. The C-terminal tail of ω-Aga IVA appears to assume a ß-turn like conformation within micelles, though it is disordered in water. Whole-cell patch clamp studies with several ω-Aga IVA analogs indicate that both the hydrophobic C-terminal tail and an Arg patch in the core region of ω-Aga IVA are critical for Cav2.1 blockade. These results suggest that the membrane environment stabilizes the structure of the toxin, enabling it to act in a manner similar to other gating modifier toxins, though its mode of interaction with the membrane and the channel is unique.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células de Purkinje
/
Membrana Celular
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Canais de Cálcio Tipo N
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ômega-Agatoxina IVA
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Bicamadas Lipídicas
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article