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Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex
by
Gu, Shenyan
, Zhou, Jie
, Rumpel, Sophie
, Strotmeier, Jasmin
, Shoemaker, Charles B.
, Perry, Kay
, Bigalke, Hans
, Rummel, Andreas
, Jin, Rongsheng
in
60 APPLIED LIFE SCIENCES
/ Amino Acid Sequence
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - metabolism
/ BASIC BIOLOGICAL SCIENCES
/ Binding Sites
/ Biochemistry
/ Biological and medical sciences
/ botulinum toxin
/ Botulinum Toxins, Type A - chemistry
/ Botulinum Toxins, Type A - metabolism
/ CLOSTRIDIUM
/ CRYSTAL STRUCTURE
/ Crystalline structure
/ Crystallography, X-Ray
/ DESIGN
/ Drug interactions
/ DRUGS
/ FOOD
/ Food contamination
/ FUNCTIONALS
/ Fundamental and applied biological sciences. Psychology
/ gastrointestinal system
/ Hydrogen-Ion Concentration
/ INGESTION
/ Intoxication
/ Medical research
/ Models, Molecular
/ Molecular biophysics
/ Molecular Sequence Data
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - metabolism
/ Mutagenesis
/ Neurons
/ Neurotoxins
/ ORAL ADMINISTRATION
/ POISONING
/ Poisons
/ Protein Binding
/ Protein Conformation
/ Protein Interaction Domains and Motifs
/ Protein Structure, Secondary
/ PROTEINS
/ Receptors
/ RESIDUES
/ SHIELDS
/ Structure in molecular biology
/ Toxins
2012
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Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex
by
Gu, Shenyan
, Zhou, Jie
, Rumpel, Sophie
, Strotmeier, Jasmin
, Shoemaker, Charles B.
, Perry, Kay
, Bigalke, Hans
, Rummel, Andreas
, Jin, Rongsheng
in
60 APPLIED LIFE SCIENCES
/ Amino Acid Sequence
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - metabolism
/ BASIC BIOLOGICAL SCIENCES
/ Binding Sites
/ Biochemistry
/ Biological and medical sciences
/ botulinum toxin
/ Botulinum Toxins, Type A - chemistry
/ Botulinum Toxins, Type A - metabolism
/ CLOSTRIDIUM
/ CRYSTAL STRUCTURE
/ Crystalline structure
/ Crystallography, X-Ray
/ DESIGN
/ Drug interactions
/ DRUGS
/ FOOD
/ Food contamination
/ FUNCTIONALS
/ Fundamental and applied biological sciences. Psychology
/ gastrointestinal system
/ Hydrogen-Ion Concentration
/ INGESTION
/ Intoxication
/ Medical research
/ Models, Molecular
/ Molecular biophysics
/ Molecular Sequence Data
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - metabolism
/ Mutagenesis
/ Neurons
/ Neurotoxins
/ ORAL ADMINISTRATION
/ POISONING
/ Poisons
/ Protein Binding
/ Protein Conformation
/ Protein Interaction Domains and Motifs
/ Protein Structure, Secondary
/ PROTEINS
/ Receptors
/ RESIDUES
/ SHIELDS
/ Structure in molecular biology
/ Toxins
2012
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Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex
by
Gu, Shenyan
, Zhou, Jie
, Rumpel, Sophie
, Strotmeier, Jasmin
, Shoemaker, Charles B.
, Perry, Kay
, Bigalke, Hans
, Rummel, Andreas
, Jin, Rongsheng
in
60 APPLIED LIFE SCIENCES
/ Amino Acid Sequence
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - metabolism
/ BASIC BIOLOGICAL SCIENCES
/ Binding Sites
/ Biochemistry
/ Biological and medical sciences
/ botulinum toxin
/ Botulinum Toxins, Type A - chemistry
/ Botulinum Toxins, Type A - metabolism
/ CLOSTRIDIUM
/ CRYSTAL STRUCTURE
/ Crystalline structure
/ Crystallography, X-Ray
/ DESIGN
/ Drug interactions
/ DRUGS
/ FOOD
/ Food contamination
/ FUNCTIONALS
/ Fundamental and applied biological sciences. Psychology
/ gastrointestinal system
/ Hydrogen-Ion Concentration
/ INGESTION
/ Intoxication
/ Medical research
/ Models, Molecular
/ Molecular biophysics
/ Molecular Sequence Data
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - metabolism
/ Mutagenesis
/ Neurons
/ Neurotoxins
/ ORAL ADMINISTRATION
/ POISONING
/ Poisons
/ Protein Binding
/ Protein Conformation
/ Protein Interaction Domains and Motifs
/ Protein Structure, Secondary
/ PROTEINS
/ Receptors
/ RESIDUES
/ SHIELDS
/ Structure in molecular biology
/ Toxins
2012
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Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex
Journal Article
Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex
2012
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Overview
Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostrídium botulinum-contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it upon entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologies.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - metabolism
/ Biological and medical sciences
/ Botulinum Toxins, Type A - chemistry
/ Botulinum Toxins, Type A - metabolism
/ DESIGN
/ DRUGS
/ FOOD
/ Fundamental and applied biological sciences. Psychology
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - metabolism
/ Neurons
/ Poisons
/ Protein Interaction Domains and Motifs
/ Protein Structure, Secondary
/ PROTEINS
/ RESIDUES
/ SHIELDS
/ Structure in molecular biology
/ Toxins
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