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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
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| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/15/7/430 |
| _version_ | 1797587344552886272 |
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| author | Tomas B. Voisin Emma C. Couves Edward W. Tate Doryen Bubeck |
| author_facet | Tomas B. Voisin Emma C. Couves Edward W. Tate Doryen Bubeck |
| author_sort | Tomas B. Voisin |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T00:34:53Z |
| format | Article |
| id | doaj.art-13649c1349d443119008cb6bad20ff67 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-11T00:34:53Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-13649c1349d443119008cb6bad20ff672023-11-18T21:38:04ZengMDPI AGToxins2072-66512023-06-0115743010.3390/toxins15070430Dynamics and Molecular Interactions of GPI-Anchored CD59Tomas B. Voisin0Emma C. Couves1Edward W. Tate2Doryen Bubeck3Department of Life Sciences, Sir Ernst Chain Building, Imperial College London, London SW7 2AZ, UKDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London SW7 2AZ, UKDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, London W12 0BZ, UKDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London SW7 2AZ, UKCD59 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.https://www.mdpi.com/2072-6651/15/7/430MACPFpore-forming proteincomplementcholesterol-dependent cytolysinsCDCmembrane attack complex |
| spellingShingle | Tomas B. Voisin Emma C. Couves Edward W. Tate Doryen Bubeck Dynamics and Molecular Interactions of GPI-Anchored CD59 Toxins MACPF pore-forming protein complement cholesterol-dependent cytolysins CDC membrane attack complex |
| 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 | MACPF pore-forming protein complement cholesterol-dependent cytolysins CDC membrane attack complex |
| url | https://www.mdpi.com/2072-6651/15/7/430 |
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