Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus

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• 作者：Pallaghy ; Paul K. ; Alewood ; Dianne ; Alewood ; Paul F. ; Norton ; Raymond S.
• 关键词：Neurotoxic polypeptide (robustoxin) ; Nuclear magnetic resonance spectroscopy ; Structure ; Cystine knot ; Beta-sheet ; Funnel-web spider ; RBX ; robustoxin from Atrax robustus ; DQF-COSY ; double quantum filtered 2D correlated spectroscopy ; E-COSY ; exclusive corr
• 刊名：FEBS Letters
• 出版年：1997
• 出版时间：December 15, 1997
• 年：1997
• 卷：419
• 期：2-3
• 页码：191-196
• 全文大小：673 K

文摘

The solution structure of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, has been determined from 2D ¹H NMR data. Robustoxin is a polypeptide of 42 residues cross-linked by four disulphide bonds, the connectivities of which were determined from NMR data and trial structure calculations to be 1–15, 8–20, 14–31 and 16–42 (a 1–4/2–6/3–7/5–8 pattern). The structure consists of a small three-stranded, anti-parallel β-sheet and a series of interlocking γ-turns at the C-terminus. It also contains a cystine knot, thus placing it in the inhibitor cystine knot motif family of structures, which includes the ω-conotoxins and a number of plant and animal toxins and protease inhibitors. Robustoxin contains three distinct charged patches on its surface, and an extended loop that includes several aromatic and non-polar residues. Both of these structural features may play a role in its binding to the voltage-gated sodium channel.