Title:The Structural Role of Gangliosides: Insights from X-ray Scattering on Model Membranes
Volume: 27
Issue: 38
Author(s): Konstantin Andreev *
Affiliation:
- Howard Hughes Medical Institute, Northwestern University, Evanston IL,United States
Keywords:
Gangliosides, Langmuir monolayers, X-ray scattering, lipid membrane, cholera toxin, sialic acid,
cancer.
Abstract:
Background: Gangliosides are an essential component of eukaryotic plasma membranes
implicated in multiple physiological processes. Little is known about molecular mechanisms underlying
the distribution and functions of membrane gangliosides. The overwhelmingly complex organization of
glycocalyx impedes the structural analysis on cell surface and the interplay between the lipid components.
Advanced X-ray analytical tools applicable to studying biological interfaces call for the simplistic
models that mimic ganglioside-enriched cellular membranes.
Objective: To summarize the mechanistic evidences of ganglioside interactions with lipid environment
and biologically active ligands using high-resolution synchrotron X-ray scattering.
Methods: A comprehensive review of studies published over the last decade was done to discuss recent
accomplishments and future trends.
Results: Langmuir monolayers represent an adequate model system to assess the effect of gangliosides
on membrane structure. Grazing incidence X-ray diffraction reveals a condensation effect by gangliosides
on zwitterionic phospholipids with the cooperative packing of sialo- and phosphate groups. In
turn, the arrangement of negatively charged lipids in ganglioside mixture remains unchanged due to the
stretched conformation of carbohydrate moieties. Upon interaction with biological ligands, such as
cholera toxin and galectins, the ganglioside redistribution within the ordered regions of monolayer follows
distinct mechanistic patterns. The cholera toxin pentamer attached to the oligosaccharide core
induces local transition from oblique to the hexagonal lattice resulting in phase coexistence. The incorporation
of the A subunit responsible for endocytosis is further promoted by the acidic environment
characteristic for endosomal space. X-ray reflectivity shows in-plane orientation of galectin dimers
with the spatial mismatch between the lectin binding sites and ganglioside carbohydrates to perturb
ceramide alkyl chains. Recent data also demonstrate sialic acid groups to be potential targets for novel
peptide mimicking anticancer therapeutics.
Conclusion: Coupled with surface X-ray scattering, the membrane mimetic approach allows for better
understanding the biological role of gangliosides and their potential applications.
