Dynamics and molecular interactions of GPI-anchored CD59
File(s)
Author(s)
Voisin, Tomas B
Couves, Emma C
Tate, Edward W
Bubeck, Doryen
Type
Journal Article
Abstract
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.
Date Issued
2023-07
Date Acceptance
2023-06-26
Citation
Toxins, 2023, 15 (7)
ISSN
2072-6651
Publisher
MDPI AG
Journal / Book Title
Toxins
Volume
15
Issue
7
Copyright Statement
© 2023 by the authors. 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/).
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:001036345400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
BINDING
CDC
CHOLESTEROL-DEPENDENT CYTOLYSIN
cholesterol-dependent cytolysins
complement
COMPLEMENT REGULATORY PROTEIN
Food Science & Technology
GPI anchor
INSERTION
INTERMEDILYSIN
Life Sciences & Biomedicine
MACPF
membrane attack complex
pore-forming protein
RECEPTOR
RECOGNITION
Science & Technology
SOFTWARE NEWS
STRUCTURAL BASIS
SYSTEM
Toxicology
Publication Status
Published
Article Number
430
Date Publish Online
2023-06-30