2mzg

Purotoxin-2 NMR structure in DPC micelles

spinqualitylabelsall models 2mzg Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mzg is a 1 chain structure with sequence from Alopecosa marikovskyi. 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 TXPR2_ALOMR Enhances the high-affinity desensitization of human P2RX3 purinoceptors (PubMed:22842000). At 50 nM, the toxin decreases the IC(50) for ambient ATP from 2.67 nM to 0.77 nM in human P2RX3 (PubMed:22842000). Publication Abstract from PubMed Traditionally, arachnid venoms are known to contain two particularly important groups of peptide toxins. One is disulfide-rich neurotoxins with a predominance of beta-structure that specifically target protein receptors in neurons or muscle cells. The other is linear cationic cytotoxins that form amphiphilic alpha-helices and exhibit rather non-specific membrane-damaging activity. In the present paper, we describe the first 3D structure of a modular arachnid toxin, purotoxin-2 (PT2) from the wolf spider Alopecosa marikovskyi (Lycosidae), studied by NMR spectroscopy. PT2 is composed of an N-terminal inhibitor cystine knot (ICK, or knottin) beta-structural domain and a C-terminal linear cationic domain. In aqueous solution, the C-terminal fragment is hyper-flexible, whereas the knottin domain is very rigid. In membrane-mimicking environment, the C-terminal domain assumes a stable amphipathic alpha-helix. This helix effectively tethers the toxin to membranes and serves as a membrane-access and membrane-anchoring device. Sequence analysis reveals that the knottin + alpha-helix architecture is quite widespread among arachnid toxins, and PT2 is therefore the founding member of a large family of polypeptides with similar structure motifs. Toxins from this family target different membrane receptors such as P2X in the case of PT2 and calcium channels, but their mechanism of action through membrane access may be strikingly similar. Structure of purotoxin-2 from wolf spider: modular design and membrane-assisted mode of action in arachnid toxins.,Oparin PB, Nadezhdin KD, Berkut AA, Arseniev AS, Grishin EV, Vassilevski AA Biochem J. 2016 Oct 1;473(19):3113-26. doi: 10.1042/BCJ20160573. Epub 2016 Jul, 13. PMID:27412961 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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