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.
Using small angle X-ray and neutron scattering and theoretical modelling we have elucidated the structure of the antimicrobial peptide, indolicidin, and the interaction with model lipid membranes of different anionic lipid compositions mimicking charge densities found in the cytoplasmic membrane of bacteria.
Lipid nanodiscs formed
by mixtures of styrene maleic acid (SMA)
copolymers and lipid membranes are important tools for studying membrane
proteins in many biotechnological applications. However, molecular
interactions leading up to their formation are not well understood.
Here, we elucidate the nanodisc formation pathways for SMA/lipid vesicle
mixtures using small-angle X-ray scattering (SAXS) that allows detailed
in situ nanostructural information. SMA copolymer that is initially
aggregated in solution inserts its styrene units into the lipid bilayer
hydrocarbon region, leading to fractures in the membrane. The initial
copolymer–lipid interactions observed in the vesicles are also
present in the formed discs, with excess copolymer distributed along
the normal of the bilayer. The size and SMA distribution in the resulting
discs strongly depend on the temperature, lipid/copolymer ratio, and
lipid type. We find that the solubilization limit increases for membranes
above the melting point, suggesting that defects in gel-like lipid
membranes play a significant role in membrane fracturing and nanodisc
formation. These findings provide unique insights into the formation
of nanodiscs as well as into the microscopic mechanism of solubilization,
which plays an important role in many applications and products ranging
from household goods to biotechnology and medicine.
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