Proteopedia

1qdp

SOLUTION STRUCTURE OF ROBUSTOXIN, THE LETHAL NEUROTOXIN FROM THE FUNNEL WEB SPIDER ATRAX ROBUSTUS, NMR, 20 STRUCTURESSOLUTION STRUCTURE OF ROBUSTOXIN, THE LETHAL NEUROTOXIN FROM THE FUNNEL WEB SPIDER ATRAX ROBUSTUS, NMR, 20 STRUCTURES

Structural highlights

1qdp is a 1 chain structure with sequence from Atrax robustus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 20 models
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TXDT1_ATRRO Inhibits tetrodotoxin-sensitive voltage-gated sodium channels (Nav) by binding to site 3. It slows the inactivation, causes a prolongation of action potential duration resulting in repetitive firing in autonomic and motor nerve fibers. Does not depolarize the resting potential. Does not affect tetrodotoxin-resistant sodium channels. This lethal neurotoxin is active on both insect and mammalian voltage-gated sodium channels.[1] [2] [3] [4]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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 beta-sheet and a series of interlocking gamma-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 omega-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.

Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus.,Pallaghy PK, Alewood D, Alewood PF, Norton RS FEBS Lett. 1997 Dec 15;419(2-3):191-6. PMID:9428632[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Mylecharane EJ, Spence I, Sheumack DD, Claassens R, Howden ME. Actions of robustoxin, a neurotoxic polypeptide from the venom of the male funnel-web spider (Atrax robustus), in anaesthetized monkeys. Toxicon. 1989;27(4):481-92. PMID:2728033
  2. ↑ Alewood D, Birinyi-Strachan LC, Pallaghy PK, Norton RS, Nicholson GM, Alewood PF. Synthesis and characterization of delta-atracotoxin-Ar1a, the lethal neurotoxin from venom of the Sydney funnel-web spider (Atrax robustus). Biochemistry. 2003 Nov 11;42(44):12933-40. PMID:14596608 doi:http://dx.doi.org/10.1021/bi030091n
  3. ↑ Little MJ, Wilson H, Zappia C, Cestele S, Tyler MI, Martin-Eauclaire MF, Gordon D, Nicholson GM. Delta-atracotoxins from Australian funnel-web spiders compete with scorpion alpha-toxin binding on both rat brain and insect sodium channels. FEBS Lett. 1998 Nov 20;439(3):246-52. PMID:9845331
  4. ↑ Nicholson GM, Walsh R, Little MJ, Tyler MI. Characterisation of the effects of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, on sodium channel activation and inactivation. Pflugers Arch. 1998 Jun;436(1):117-26. PMID:9560455
  5. ↑ Pallaghy PK, Alewood D, Alewood PF, Norton RS. Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus. FEBS Lett. 1997 Dec 15;419(2-3):191-6. PMID:9428632
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