View source for 4gv5


==X-ray structure of crotamine, a cell-penetrating peptide from the Brazilian snake Crotalus durissus terrificus==
<StructureSection load='4gv5' size='340' side='right'caption='[[4gv5]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gv5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Crotalus_durissus_terrificus Crotalus durissus terrificus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GV5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gv5 OCA], [https://pdbe.org/4gv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gv5 RCSB], [https://www.ebi.ac.uk/pdbsum/4gv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gv5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MYC2_CRODU MYC2_CRODU] Cationic peptide that possesses multiple functions. It acts as a cell-penetrating peptide (CPP), and as a potent voltage-gated potassium channel inhibitor. It exhibits antimicrobial activities, hind limb paralysis, and severe muscle necrosis by a non-enzymatic mechanism. As a cell-penetrating peptide, crotamine has high specificity for actively proliferating cells, and interacts inside the cell with subcellular and subnuclear structures, like vesicular compartments, chromosomes and centrioles. It penetrates into the cells as fast as five minutes after its addition to cell culture medium (PubMed:18662711). In vivo, after intraperitoneal administration, it is found in cells of peritoneal fluid and bone marrow, demonstrating preferential nuclear and perinuclear localization. To enter the cell, it interacts with the chains of heparan sulfate membrane proteoglycan (HSPG), and is endocytosed (in complex with HSPG) in vesicles which are transported into the cell with the help of clathrin. Inside the cell, crotamine accumulates in lysosomal vesicles. As soon as the peptide accumulates in endosomes/lysosomes vesicles, these compartments are disrupted and their contents released into the cytosol. This loss of lysosomal content induces cell death at high concentrations, or promotes the distribution of crotamine in cytoplasmic compartments, which is a step before crotamine nuclear uptake (PubMed:15231729, PubMed:17491023). As a potassium channel inhibitor, this toxin selectively inhibits Kv1.1/KCNA1, Kv1.2/KCNA2 and Kv1.3/KCNA3 channels with an IC(50) of 369, 386 and 287 nM, respectively (PubMed:22498659). The inhibition of Kv1.3/KCNA channels induced by this toxin occurs rapidly and is voltage-independent. The channel inhibition is reversible after washing, suggesting a pure and classical channel blockage effect, without effects in potassium channel kinetics (PubMed:22498659). As an antimicrobial peptide, crotamine shows antibacterial activity against E.coli and B.subtilis, and antifungal activity against Candida spp., Trichosporon spp. and C.neoformans. It kills bacteria through membrane permeabilization.<ref>PMID:1176086</ref> <ref>PMID:15231729</ref> <ref>PMID:17491023</ref> <ref>PMID:17588630</ref> <ref>PMID:18662711</ref> <ref>PMID:19706485</ref> <ref>PMID:21386851</ref> <ref>PMID:22142367</ref> <ref>PMID:22498659</ref> <ref>PMID:23022146</ref> <ref>PMID:667499</ref> <ref>PMID:9839677</ref> 
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== Publication Abstract from PubMed ==
The crystal structure of the myotoxic, cell-penetrating, basic polypeptide crotamine isolated from the venom of Crotalus durissus terrificus has been determined by single-wavelength anomalous dispersion techniques and refined at 1.7 A resolution. The structure reveals distinct cationic and hydrophobic surface regions that are located on opposite sides of the molecule. This surface-charge distribution indicates its possible mode of interaction with negatively charged phospholipids and other molecular targets to account for its diverse pharmacological activities. Although the sequence identity between crotamine and human beta-defensins is low, the three-dimensional structures of these functionally related peptides are similar. Since crotamine is a leading member of a large family of myotoxic peptides, its structure will provide a basis for the design of novel cell-penetrating molecules.

Structure of the polypeptide crotamine from the Brazilian rattlesnake Crotalus durissus terrificus.,Coronado MA, Gabdulkhakov A, Georgieva D, Sankaran B, Murakami MT, Arni RK, Betzel C Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):1958-64. doi:, 10.1107/S0907444913018003. Epub 2013 Sep 20. PMID:24100315<ref>PMID:24100315</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4gv5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Crotamine|Crotamine]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Crotalus durissus terrificus]]
[[Category: Large Structures]]
[[Category: Arni RK]]
[[Category: Betzel C]]
[[Category: Coronado MA]]
[[Category: Gabdulkhakov A]]
[[Category: Georgieva D]]
[[Category: Murakami MT]]
[[Category: Sankaran B]]