The importance of side branches of glycosylphosphatidylinositol anchors
- Many proteins are anchored to the cell surface of eukaryotes using a unique family of glycolipids called glycosylphosphatidylinositol (GPI) anchors.
These glycolipids also exist without a covalently bound protein, in particular on the cell surfaces of protozoan parasites where they are densely populated.
GPIs and GPI-anchored proteins participate in multiple cellular processes such as signal transduction, cell adhesion, protein trafficking and pathogenesis of Malaria, Toxoplasmosis, Trypanosomiasis and prion diseases, among others.
All GPIs share a common conserved glycan core modified in a cell-dependent manner with additional side glycans or phosphoethanolamine residues. Here, we use atomistic molecular dynamic simulations and perform a systematic study to evaluate the structural properties of GPIs with different side chains inserted in lipid bilayers.
Our results show a flop-down orientation of GPIs with respect to the membrane surface and the presentation of the side chain residues to the solvent.
This finding agreesMany proteins are anchored to the cell surface of eukaryotes using a unique family of glycolipids called glycosylphosphatidylinositol (GPI) anchors.
These glycolipids also exist without a covalently bound protein, in particular on the cell surfaces of protozoan parasites where they are densely populated.
GPIs and GPI-anchored proteins participate in multiple cellular processes such as signal transduction, cell adhesion, protein trafficking and pathogenesis of Malaria, Toxoplasmosis, Trypanosomiasis and prion diseases, among others.
All GPIs share a common conserved glycan core modified in a cell-dependent manner with additional side glycans or phosphoethanolamine residues. Here, we use atomistic molecular dynamic simulations and perform a systematic study to evaluate the structural properties of GPIs with different side chains inserted in lipid bilayers.
Our results show a flop-down orientation of GPIs with respect to the membrane surface and the presentation of the side chain residues to the solvent.
This finding agrees well with experiments showing the role of the side residues as active epitopes for recognition of GPIs by macrophages and induction of GPI-glycan-specific immune responses.
Protein-GPI interactions were investigated by attaching parasitic GPIs to Green Fluorescent Protein. GPIs are observed to recline on the membrane surface and pull down the attached protein close to the membrane facilitating mutual contacts between protein, GPI and the lipid bilayer.
This model is efficient in evaluating the interaction of GPIs and GPI-anchored proteins with membranes and can be extended to study other parasitic GPIs and proteins and develop GPI-based immunoprophylaxis to treat infectious diseases.…
Verfasserangaben: | Pallavi BanerjeeORCiDGND, Daniel Varon SilvaGND, Reinhard LipowskyORCiDGND, Mark Santer |
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DOI: | https://doi.org/10.1093/glycob/cwac037 |
ISSN: | 1460-2423 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/36197124 |
Titel des übergeordneten Werks (Englisch): | Glycobiology |
Untertitel (Englisch): | a molecular dynamics perspective |
Verlag: | Oxford Univ. Press |
Verlagsort: | Cary |
Publikationstyp: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Erstveröffentlichung: | 03.10.2022 |
Erscheinungsjahr: | 2022 |
Datum der Freischaltung: | 02.08.2024 |
Freies Schlagwort / Tag: | GFP; GPI; conformation; glycan recognition; molecular dynamics |
Band: | 32 |
Ausgabe: | 11 |
Seitenanzahl: | 16 |
Erste Seite: | 933 |
Letzte Seite: | 948 |
Fördernde Institution: | Max Planck Society; Max-Planck-RIKEN joint center in Systems Chemical; Biology; International Max Planck Research School (IMPRS) for Multiscale; Bio-systems |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Peer Review: | Referiert |
Publikationsweg: | Open Access / Hybrid Open-Access |
Lizenz (Deutsch): | ![]() |