Membrane deformation by neolectins with engineered glycolipid binding sites

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Lectins are proteins that bind carbohydrates (glycans) on cell surfaces.
• Multivalent lectins can influence glycolipid distribution and alter cell membrane shape.
• Understanding lectin multivalency is key to deciphering cell surface interactions.

Purpose of the Study:

• To design and engineer neolectins with controlled valency and binding site arrangement.
• To investigate the role of multivalency in lectin avidity to glycosylated surfaces.
• To analyze the impact of neolectins on glycolipid-containing membrane dynamics.

Main Methods:

• Engineering of a monomeric hexavalent neolectin from a bacterial lectin template.
• Design and production of 13 neolectins with valency ranging from 0 to 6.
• Analysis of fucose binding in solution, surface attachment, and giant liposome invagination.

Main Results:

• Avidity for glycosylated surfaces requires at least two binding sites.
• Membrane bending and invagination are critically dependent on the distance between binding sites.
• Neolectin design allows for precise control over multivalency and its effects.

Conclusions:

• Lectin-induced membrane dynamics are sensitive to the spatial arrangement of binding sites.
• Neolectins provide a powerful tool to study the biophysics of lectin-glycan interactions.
• This research offers insights into the mechanisms of cell surface recognition and membrane remodeling.