|
|
|
|
Structure of a Bimodular Botulinum Neurotoxin Complex Provides Insights into Its Oral Toxicity
|
|
|
|
|
|
|
|
نویسنده
|
lee k. ,gu s. ,jin l. ,le t.t.n. ,cheng l.w. ,strotmeier j. ,kruel a.m. ,yao g. ,perry k. ,rummel a. ,jin r.
|
|
منبع
|
plos pathogens - 2013 - دوره : 9 - شماره : 10
|
|
چکیده
|
Botulinum neurotoxins (bonts) are produced by clostridium botulinum and cause the fatal disease botulism,a flaccid paralysis of the muscle. bonts are released together with several auxiliary proteins as progenitor toxin complexes (ptcs) to become highly potent oral poisons. here,we report the structure of a ∼760 kda 14-subunit large ptc of serotype a (l-ptc/a) and reveal insight into its absorption mechanism. using a combination of x-ray crystallography,electron microscopy,and functional studies,we found that l-ptc/a consists of two structurally and functionally independent sub-complexes. a hetero-dimeric 290 kda complex protects bont,while a hetero-dodecameric 470 kda complex facilitates its absorption in the harsh environment of the gastrointestinal tract. bont absorption is mediated by nine glycan-binding sites on the dodecameric sub-complex that forms multivalent interactions with carbohydrate receptors on intestinal epithelial cells. we identified monosaccharides that blocked oral bont intoxication in mice,which suggests a new strategy for the development of preventive countermeasures for bonts based on carbohydrate receptor mimicry. © 2013 lee et al.
|
|
|
|
|
آدرس
|
department of physiology and biophysics,university of california,irvine,ca, United States, department of physiology and biophysics,university of california,irvine,ca, United States, infectious and inflammatory disease center,sanford-burnham medical research institute,la jolla,ca, United States, institut für toxikologie,medizinische hochschule hannover,hannover, Germany, foodborne contaminants research unit,western regional research center,united states department of agriculture,agricultural research service,albany,ca, United States, institut für toxikologie,medizinische hochschule hannover,hannover, Germany, institut für toxikologie,medizinische hochschule hannover,hannover, Germany, department of physiology and biophysics,university of california,irvine,ca, United States, ne-cat and department of chemistry and chemical biology,cornell university,argonne national laboratory,argonne,il, United States, institut für toxikologie,medizinische hochschule hannover,hannover, Germany, department of physiology and biophysics,university of california,irvine,ca,united states,neuroscience,aging and stem cell center,sanford-burnham medical research institute,la jolla,ca, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|