Schematic of proteins constructed from the Gal-3 carbo-hydrate recognition domain (CRD). WT Gal-3 contains one CRD bound to an N-terminal domain that promotes oligomeric assembly. Several engineered variants were tested, including a truncated Gal-3 CRD lacking the N-terminal domain (trGal-3) and a Gal-3 CRD homodimer (Gal-3–Gal-3). From Vander Zanden et al., Biophysical Journal 122, 1926–1937, June 6, 2023. © 2022 Biophysical Society
This study, carried out at the Liquid Surface/Interface Scattering facility of the NSF’s ChemMatCARS at the Advanced Photon Source, Argonne National Laboratory, presents the first direct observation of Galectin-3 (Gal-3) bound to the ganglioside GM1 in a membrane. Gal-3 is a 𝞫-galactosidase-binding protein involved in various crucial biological processes, including neuronal growth and adhesion.
Gangliosides comprise any of a group of complex lipids present in the gray matter of the human brain. While the atomistic structure of Gal-3 bound to small carbohydrate ligands is known, the method by which Gal-3 binds GM1 in a membrane has been unknown, and the influence of this interaction on Gal-3 structure and oligomeric assembly has to be clarified.
This new mesoscale structural information about Gal-3/membrane interactions, attempts to close the information gap between the atomistic x-ray crystallography structures and micro-scale cell microscopy studies.
The researchers’ results show that Gal-3 forms specific interactions with GM1 glycans in a membrane thanks to a Gal-3’s highly flexible binding interface that can support the required protein-protein interactions, including oligomerization (the chemical process that converts monomers to macromolecular complexes through a finite degree of polymerization) via the N-terminal domain.
The theory is that these interactions play important roles in neuronal cell-signaling applications; these results reveal the structure-function relationship that facilitates this dynamic behavior.
Overall, this structural information is essential for understanding of biologically important Gal-3/GM1 interactions and their roles in cell communication.
Crystal M. Vander Zanden1*, Jaroslaw Majewski2,3,4, Yvonne Weissbarth1, Danielle F. Browne1, Erik B. Watkins4, and Hans-Joachim Gabius5, “Structure of Galectin-3 bound to a model membrane containing ganglioside GM1,” Biophysical Journal 122, 1926–1937, June 6, 2023. DOI: 10.1016/j.bpj.2022.08.018 1University of Colorado at Colorado Springs, 2National Science Foundation, 3University of New Mexico, 4Los Alamos National Laboratory, 5udwig-Maximilians-University Munich *Correspondence: firstname.lastname@example.org © 2022 Biophysical Society