This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
4gv5
From Proteopedia
X-ray structure of crotamine, a cell-penetrating peptide from the Brazilian snake Crotalus durissus terrificus
Structural highlights
FunctionMYC2_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.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] Publication Abstract from PubMedThe 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[13] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
