About: Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins

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About: Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins
Creator	Cui, Hong Julien, Jean-Philippe Rubinstein, John Beilhartz, Greg Kucharska, Iga Lee, Hunsang Liang, Huazhu Melnyk, Roman Raman, Swetha Schramek, Daniel Taipale, Mikko Hiu, Mandy Lam, Yi
Source	Elsevier; Medline; PMC
abstract	Pathogenic clostridial species secrete potent toxins that induce severe host tissue damage. Paeniclostridium sordellii lethal toxin (TcsL) causes an almost invariably lethal toxic shock syndrome associated with gynecological infections. TcsL is 87% similar to C. difficile TcdB, which enters host cells via Frizzled receptors in colon epithelium. However, P. sordellii infections target vascular endothelium, suggesting that TcsL exploits another receptor. Here, using CRISPR/Cas9 screening, we establish semaphorins SEMA6A and SEMA6B as TcsL receptors. We demonstrate that recombinant SEMA6A can protect mice from TcsL-induced edema. A 3.3 Å cryo-EM structure shows that TcsL binds SEMA6A with the same region that in TcdB binds structurally unrelated Frizzled. Remarkably, 15 mutations in this evolutionarily divergent surface are sufficient to switch binding specificity of TcsL to that of TcdB. Our findings establish semaphorins as physiologically relevant receptors for TcsL and reveal the molecular basis for the difference in tissue targeting and disease pathogenesis between highly related toxins.
has issue date	2020-06-25(xsd:dateTime)
bibo:doi	10.1016/j.cell.2020.06.005
bibo:pmid	32589945
has license	no-cc
sha1sum (hex)	dfa9e5a7a9e5cc3e0df0a5d3e54e04a993b48b16
schema:url	https://doi.org/10.1016/j.cell.2020.06.005
resource representing a document's title	Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins
has PubMed Central identifier	PMC7316060
has PubMed identifier	32589945
schema:publication	Cell
resource representing a document's body	covid:dfa9e5a7a9e5cc3e0df0a5d3e54e04a993b48b16#body_text
is schema:about of	named entity 'lethal' named entity 'Correspondence' named entity 'BINDING' named entity 'Highlights' named entity 'interaction' named entity 'screen' named entity 'Graphical' named entity 'Semaphorin' named entity 'lungs' named entity 'receptor' named entity 'cryo-EM' named entity 'edema' named entity 'Toxins' named entity 'Semaphorin' named entity 'Receptor Specificity' named entity 'SEMA6A' named entity 'SEMA6A' named entity 'axon guidance' named entity 'toxicity' named entity 'acute toxicity' named entity 'TcdB' named entity 'SEMA6A' named entity 'amino acid' named entity 'cytotoxin' named entity 'mutants' named entity 'toxin' named entity 'fluid in the lungs' named entity 'SEMA6A' named entity 'hydrogen bond' named entity 'anaerobic' named entity 'Mice' named entity 'standard deviations' named entity 'steric clashes' named entity 'toxin' named entity 'gRNAs' named entity 'evolution' named entity 'SEMA' named entity 'asymptomatic' named entity 'SEMA6C' named entity 'SEMA6A' named entity 'central nervous' named entity 'cell lines' named entity 'childbirth' named entity 'Plexin' named entity 'SEMA6A' named entity 'Plexin' named entity 'UDP-glucose pyrophosphorylase' named entity 'SEMA6A' named entity 'TcdB' named entity 'host organisms' named entity 'ligands' named entity 'toxin' named entity 'cell function' named entity 'C. perfringens' named entity 'cryo-EM' named entity 'SEMA6A' named entity 'SEMA6C' named entity 'SEMA6A' named entity 'viral proteins' named entity 'monomers' named entity 'genome' named entity 'Frizzled' named entity 'TcdB' named entity 'toxin' named entity 'FZD7' named entity 'clostridial' named entity 'Cas9' named entity 'SEMA6A' named entity 'SEMA6A'

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