Cargando…

Dynamics and Molecular Interactions of GPI-Anchored CD59

CD59 is a GPI-anchored cell surface receptor that serves as a gatekeeper to controlling pore formation. It is the only membrane-bound inhibitor of the complement membrane attack complex (MAC), an immune pore that can damage human cells. While CD59 blocks MAC pores, the receptor is co-opted by bacter...

Descripción completa

Detalles Bibliográficos
Autores principales: Voisin, Tomas B., Couves, Emma C., Tate, Edward W., Bubeck, Doryen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10467114/
https://www.ncbi.nlm.nih.gov/pubmed/37505699
http://dx.doi.org/10.3390/toxins15070430
_version_ 1785099042779299840
author Voisin, Tomas B.
Couves, Emma C.
Tate, Edward W.
Bubeck, Doryen
author_facet Voisin, Tomas B.
Couves, Emma C.
Tate, Edward W.
Bubeck, Doryen
author_sort Voisin, Tomas B.
collection PubMed
description CD59 is a GPI-anchored cell surface receptor that serves as a gatekeeper to controlling pore formation. It is the only membrane-bound inhibitor of the complement membrane attack complex (MAC), an immune pore that can damage human cells. While CD59 blocks MAC pores, the receptor is co-opted by bacterial pore-forming proteins to target human cells. Recent structures of CD59 in complexes with binding partners showed dramatic differences in the orientation of its ectodomain relative to the membrane. Here, we show how GPI-anchored CD59 can satisfy this diversity in binding modes. We present a PyLipID analysis of coarse-grain molecular dynamics simulations of a CD59-inhibited MAC to reveal residues of complement proteins (C6:Y285, C6:R407 C6:K412, C7:F224, C8β:F202, C8β:K326) that likely interact with lipids. Using modules of the MDAnalysis package to investigate atomistic simulations of GPI-anchored CD59, we discover properties of CD59 that encode the flexibility necessary to bind both complement proteins and bacterial virulence factors.
format Online
Article
Text
id pubmed-10467114
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-104671142023-08-31 Dynamics and Molecular Interactions of GPI-Anchored CD59 Voisin, Tomas B. Couves, Emma C. Tate, Edward W. Bubeck, Doryen Toxins (Basel) Article CD59 is a GPI-anchored cell surface receptor that serves as a gatekeeper to controlling pore formation. It is the only membrane-bound inhibitor of the complement membrane attack complex (MAC), an immune pore that can damage human cells. While CD59 blocks MAC pores, the receptor is co-opted by bacterial pore-forming proteins to target human cells. Recent structures of CD59 in complexes with binding partners showed dramatic differences in the orientation of its ectodomain relative to the membrane. Here, we show how GPI-anchored CD59 can satisfy this diversity in binding modes. We present a PyLipID analysis of coarse-grain molecular dynamics simulations of a CD59-inhibited MAC to reveal residues of complement proteins (C6:Y285, C6:R407 C6:K412, C7:F224, C8β:F202, C8β:K326) that likely interact with lipids. Using modules of the MDAnalysis package to investigate atomistic simulations of GPI-anchored CD59, we discover properties of CD59 that encode the flexibility necessary to bind both complement proteins and bacterial virulence factors. MDPI 2023-06-30 /pmc/articles/PMC10467114/ /pubmed/37505699 http://dx.doi.org/10.3390/toxins15070430 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Voisin, Tomas B.
Couves, Emma C.
Tate, Edward W.
Bubeck, Doryen
Dynamics and Molecular Interactions of GPI-Anchored CD59
title Dynamics and Molecular Interactions of GPI-Anchored CD59
title_full Dynamics and Molecular Interactions of GPI-Anchored CD59
title_fullStr Dynamics and Molecular Interactions of GPI-Anchored CD59
title_full_unstemmed Dynamics and Molecular Interactions of GPI-Anchored CD59
title_short Dynamics and Molecular Interactions of GPI-Anchored CD59
title_sort dynamics and molecular interactions of gpi-anchored cd59
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10467114/
https://www.ncbi.nlm.nih.gov/pubmed/37505699
http://dx.doi.org/10.3390/toxins15070430
work_keys_str_mv AT voisintomasb dynamicsandmolecularinteractionsofgpianchoredcd59
AT couvesemmac dynamicsandmolecularinteractionsofgpianchoredcd59
AT tateedwardw dynamicsandmolecularinteractionsofgpianchoredcd59
AT bubeckdoryen dynamicsandmolecularinteractionsofgpianchoredcd59