High-Resolution Crystal Structures Elucidate the Molecular Basis of Cholera Blood Group Dependence

Autor: Ute Krengel, Vesna Hodnik, Daniel Burschowsky, Victoria Ariel Bjørnestad, Gregor Anderluh, Julie Elisabeth Heggelund
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Bacterial Diseases
Protein Conformation
Physiology
medicine.disease_cause
Crystallography
X-Ray
Toxicology
Pathology and Laboratory Medicine
El Tor
Biochemistry
Protein structure
Cholera
Immune Physiology
Medicine and Health Sciences
Toxins
Receptor
lcsh:QH301-705.5
Crystallography
Immune System Proteins
biology
Physics
Cholera toxin
Hematology
Condensed Matter Physics
Body Fluids
Blood
Infectious Diseases
Milk
Physical Sciences
Crystal Structure
Anatomy
Research Article
Neglected Tropical Diseases
lcsh:Immunologic diseases. Allergy
Cholera Toxin
Molecular Sequence Data
Toxic Agents
Immunology
Microbiology
ABO Blood-Group System
03 medical and health sciences
Antigen
Virology
ABO blood group system
Genetics
medicine
Electron Density
Humans
Solid State Physics
Antigens
Molecular Biology
Base Sequence
Toxin
Biology and Life Sciences
Proteins
Surface Plasmon Resonance
medicine.disease
biology.organism_classification
Tropical Diseases
Mucus
030104 developmental biology
lcsh:Biology (General)
Parasitology
lcsh:RC581-607
Blood Groups
Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 12, Iss 4, p e1005567 (2016)
'PLoS Pathogens ', vol: 12, pages: e1005567-1-e1005567-19 (2016)
ISSN: 1553-7366
1553-7374
Popis: Cholera is the prime example of blood-group-dependent diseases, with individuals of blood group O experiencing the most severe symptoms. The cholera toxin is the main suspect to cause this relationship. We report the high-resolution crystal structures (1.1–1.6 Å) of the native cholera toxin B-pentamer for both classical and El Tor biotypes, in complexes with relevant blood group determinants and a fragment of its primary receptor, the GM1 ganglioside. The blood group A determinant binds in the opposite orientation compared to previously published structures of the cholera toxin, whereas the blood group H determinant, characteristic of blood group O, binds in both orientations. H-determinants bind with higher affinity than A-determinants, as shown by surface plasmon resonance. Together, these findings suggest why blood group O is a risk factor for severe cholera.
Author Summary Cholera is a severe diarrheal disease that kills a hundred thousand people per year. With climate change, the number of cases is predicted to increase to millions. Individuals with blood group O are particularly at risk. Here we report high-resolution crystal structures of the native cholera toxin of both major biotypes, in complexes with relevant blood group determinants. These structures, in combination with quantitative binding data, shed light on cholera blood group dependence. Understanding the molecular basis of this association is expected to be of considerable importance, for example for developing new vaccination strategies that take this information into account.
Databáze: OpenAIRE
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