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

Julie Elisabeth Heggelund; Daniel Burschowsky; Victoria Ariel Bjørnestad; Vesna Hodnik; Gregor Anderluh; Ute Krengel

doi:10.1371/journal.ppat.1005567

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

PLoS Pathog. 2016 Apr 15;12(4):e1005567. doi: 10.1371/journal.ppat.1005567. eCollection 2016 Apr.

Authors

Julie Elisabeth Heggelund¹, Daniel Burschowsky¹, Victoria Ariel Bjørnestad¹, Vesna Hodnik², Gregor Anderluh^{2

3}, Ute Krengel¹

Affiliations

¹ Department of Chemistry, University of Oslo, Blindern, Norway.
² Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
³ The National Institute of Chemistry, Ljubljana, Slovenia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ABO Blood-Group System / chemistry*
ABO Blood-Group System / metabolism*
Base Sequence
Cholera / blood*
Cholera Toxin / chemistry*
Cholera Toxin / metabolism*
Crystallography, X-Ray
Humans
Molecular Sequence Data
Protein Conformation
Surface Plasmon Resonance

Substances

ABO Blood-Group System
Cholera Toxin

Grants and funding

This study was financed by funds from the University of Oslo (including UiO-PES2020) and the Norwegian Research Council (grant no. 216625), received by JEH DB UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.