title: High-Resolution Crystal Structures Elucidate the Molecular Basis of Cholera Blood Group Dependence.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Oslo, Blindern, Norway.
authors.forename: Julie Elisabeth
authors.initials: JE
authors.lastname: Heggelund
authors.affiliation: Department of Chemistry, University of Oslo, Blindern, Norway.
authors.forename: Daniel
authors.initials: D
authors.lastname: Burschowsky
authors.affiliation: Department of Chemistry, University of Oslo, Blindern, Norway.
authors.forename: Victoria Ariel
authors.initials: VA
authors.lastname: Bjørnestad
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Hodnik
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.|The National Institute of Chemistry, Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Anderluh
authors.affiliation: Department of Chemistry, University of Oslo, Blindern, Norway.
authors.forename: Ute
authors.initials: U
authors.lastname: Krengel
mesh_terms: D000017:ABO Blood-Group System / Q000737:chemistry* / Q000378:metabolism*; D001483:Base Sequence; D002771:Cholera / Q000097:blood*; D002772:Cholera Toxin / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020349:Surface Plasmon Resonance
chemical_list: D000017:ABO Blood-Group System; D002772:Cholera Toxin