Zwitterionic Character and Lipid Composition Determine the Behaviour of Glycosylphosphatidylinositol Fragments in Monolayers.

Ankita Malik,Peter H Seeberger,Gerald Brezesinski,Daniel Varón Silva

doi:10.1002/cphc.202100002

Ankita Malik, Peter H Seeberger + Show 2 more

Open Access

https://doi.org/10.1002/cphc.202100002

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Abstract

Glycosylphosphatidylinositols (GPIs) are complex glycolipids found in free form or anchoring proteins to the outer leaflet of the cell membrane in eukaryotes. GPIs have been associated with the formation of lipid rafts and protein sorting on membranes. The presence of a conserved glycan core with cell‐specific modifications together with lipid remodelling during biosynthesis suggest that the properties of the glycolipids are being fine‐tuned. We synthesized a series of GPI fragments and evaluated the interactions and arrangement of these glycolipids in monolayers as a 2‐D membrane model. GIXD and IRRAS analyses showed the need of N‐acetylglucosamine deacetylation for the formation of hydrogen bonds to obtain highly structured domains in the monolayers and an effect of the unsaturated lipids in formation and localization of the glycolipids within or between membrane microdomains. These results contribute to understand the role of these glycolipids and their modifications in the organization of membranes.

Highlights

Glycosylphosphatidylinositol (GPI) are glycolipids that are attached as posttranslational modification to the C-terminus of proteins or are displayed as free glycolipids on the cell surface of eukaryotes.[1]
We evaluated the arrangement of these glycolipids in monolayers using grazing incidence X-ray diffraction (GIXD) and infrared reflection absorption spectroscopy (IRRAS)
Glycolipids 2 and 3 containing N-acetylglucosamine (Figure 2) were used to suppress the participation of the amino group in the hydrogen bond formation between the head groups leading to the formation of highly-structured phases.[13]

Summary

Introduction

Glycosylphosphatidylinositol (GPI) are glycolipids that are attached as posttranslational modification to the C-terminus of proteins or are displayed as free glycolipids (free GPIs) on the cell surface of eukaryotes.[1]. GPI-anchored proteins (GPI-APs) participate in many cellular processes on the membrane such as protein sorting and trafficking,[2] parasitic infections,[3] adhesion and nutrient uptake.[4] GPI-APs have been associated as components of lipid rafts.[5] recent reports describe the presence of GPI-APs mainly outside of lipid rafts and as obstacles for the diffusion of other membrane proteins.[6]. Protein aggregation and sorting is affected by interactions involving the glycan and lipid parts, suggesting interactions between GPI components and other membrane molecules to be responsible for the heterogeneous distribution of GPIs and GPI-anchored molecules on the cell membrane.[10]

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Discussion

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