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2018-05-02Zeitschriftenartikel DOI: 10.25646/5679
A lipid-binding loop of botulinum neurotoxin serotypes B, DC and G is an essential feature to confer their exquisite potency
dc.contributor.authorStern, Daniel
dc.contributor.authorWeisemann, Jasmin
dc.contributor.authorLe Blanc, Alexander
dc.contributor.authorvon Berg, Laura
dc.contributor.authorMahrhold, Stefan
dc.contributor.authorPiesker, Janett
dc.contributor.authorLaue, Michael
dc.contributor.authorLuppa, Peter B.
dc.contributor.authorDorner, Martin B.
dc.contributor.authorDorner, Brigitte G.
dc.contributor.authorRummel, Andreas
dc.date.accessioned2018-09-12T14:18:49Z
dc.date.available2018-09-12T14:18:49Z
dc.date.issued2018-05-02none
dc.identifier.other10.1371/journal.ppat.1007048
dc.identifier.urihttp://edoc.rki.de/176904/5744
dc.description.abstractThe exceptional toxicity of botulinum neurotoxins (BoNTs) is mediated by high avidity binding to complex polysialogangliosides and intraluminal segments of synaptic vesicle proteins embedded in the presynaptic membrane. One peculiarity is an exposed hydrophobic loop in the toxin’s cell binding domain HC, which is located between the ganglioside- and protein receptor-binding sites, and that is particularly pronounced in the serotypes BoNT/B, DC, and G sharing synaptotagmin as protein receptor. Here, we provide evidence that this HC loop is a critical component of their tripartite receptor recognition complex. Binding to nanodisc-embedded receptors and toxicity were virtually abolished in BoNT mutants lacking residues at the tip of the HC loop. Surface plasmon resonance experiments revealed that only insertion of the HC loop into the lipid-bilayer compensates for the entropic penalty inflicted by the dual-receptor binding. Our results represent a new paradigm of how BoNT/B, DC, and G employ ternary interactions with a protein, ganglioside, and lipids to mediate their extraordinary neurotoxicity.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleA lipid-binding loop of botulinum neurotoxin serotypes B, DC and G is an essential feature to confer their exquisite potencynone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:0257-176904/5744-8
dc.identifier.doihttp://dx.doi.org/10.25646/5679
dc.type.versionpublishedVersionnone
local.edoc.container-titlePLoS ONEnone
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007048none
local.edoc.container-publisher-namePublic Library of Sciencenone
local.edoc.container-volume14none
local.edoc.container-issue5none
local.edoc.container-firstpage1none
local.edoc.container-lastpage25none
local.edoc.rki-departmentZentrum für Biologische Gefahren und Spezielle Pathogenenone
dc.description.versionPeer Reviewednone

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