2e4m

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2e4m, resolution 1.85Å

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Crystal structure of hemagglutinin subcomponent complex (HA-33/HA-17) from Clostridium botulinum serotype D strain 4947

Overview

The botulinum neurotoxins (BoNTs) are the most potent toxins known in, nature, causing the lethal disease known as botulism in humans and, animals. The BoNTs act by inhibiting neurotransmitter release from, cholinergic synapses. Clostridium botulinum strains produce large BoNTs, toxin complexes, which include auxiliary non-toxic proteins that appear, not only to protect BoNTs from the hostile environment of the digestive, tract but also to assist BoNT translocation across the intestinal mucosal, layer. In this study, we visualize for the first time a series of, botulinum serotype D toxin complexes using negative stain transmission, electron microscopy (TEM). The complexes consist of the 150-kDa BoNT, 130-kDa non-toxic non-hemagglutinin (NTNHA), and three kinds of, hemagglutinin (HA) subcomponents: 70-kDa HA-70, 33-kDa HA-33, and 17-kDa, HA-17. These components assemble sequentially to form the complex. A novel, TEM image of the mature L-TC revealed an ellipsoidal-shaped structure with, "three arms" attached. The "body" section was comprised of a single BoNT, a single NTNHA and three HA-70 molecules. The arm section consisted of a, complex of HA-33 and HA-17 molecules. We determined the x-ray crystal, structure of the complex formed by two HA-33 plus one HA-17. On the basis, of the TEM image and biochemical results, we propose a novel 14-mer, subunit model for the botulinum toxin complex. This unique model suggests, how non-toxic components make up a "delivery vehicle" for BoNT.

About this Structure

2E4M is a Protein complex structure of sequences from Clostridium botulinum. Full crystallographic information is available from OCA.

Reference

A Novel Subunit Structure of Clostridium botulinum Serotype D Toxin Complex with Three Extended Arms., Hasegawa K, Watanabe T, Suzuki T, Yamano A, Oikawa T, Sato Y, Kouguchi H, Yoneyama T, Niwa K, Ikeda T, Ohyama T, J Biol Chem. 2007 Aug 24;282(34):24777-24783. Epub 2007 Jun 20. PMID:17581814

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