Imperial College London
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Dr. Doryen Bubeck

Faculty of Natural Sciences, Department of Life Sciences

Professor in Structural Immunology
 
 
 
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Contact

 

+44 (0)20 7594 2989d.bubeck Website

 
 
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Location

 

506Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Parsons:2019:10.1038/s41467-019-10058-7,
author = {Parsons, E and Stanley, G and Pyne, A and Hodel, A and Nievergelt, A and Menny, A and Yon, A and Rowley, A and Richter, R and Fantner, G and Bubeck, D and Hoogenboom, B},
doi = {10.1038/s41467-019-10058-7},
journal = {Nature Communications},
pages = {1--10},
title = {Single-molecule kinetics of pore assembly by the membrane attack complex},
url = {http://dx.doi.org/10.1038/s41467-019-10058-7},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The membrane attack complex (MAC) is a hetero-oligomeric protein assembly that kills pathogens by perforating their cell envelopes. The MAC is formed by sequential assembly of soluble complement proteins C5b, C6, C7, C8 and C9, but little is known about the rate-limiting steps in this process. Here, we use rapid atomic force microscopy (AFM) imaging to show that MAC proteins oligomerize within the membrane, unlike structurally homologous bacterial pore-forming toxins. C5b-7 interacts with the lipid bilayer prior to recruiting C8. We discover that incorporation of the first C9 is the kinetic bottleneck of MAC formation, after which rapid C9 oligomerization completes the pore. This defines the kinetic basis for MAC assembly and provides insight into how human cells are protected from bystander damage by the cell surface receptor CD59, which is offered a maximum temporal window to halt the assembly at the point of C9 insertion.
AU  - Parsons,E
AU  - Stanley,G
AU  - Pyne,A
AU  - Hodel,A
AU  - Nievergelt,A
AU  - Menny,A
AU  - Yon,A
AU  - Rowley,A
AU  - Richter,R
AU  - Fantner,G
AU  - Bubeck,D
AU  - Hoogenboom,B
DO  - 10.1038/s41467-019-10058-7
EP  - 10
PY  - 2019///
SN  - 2041-1723
SP  - 1
TI  - Single-molecule kinetics of pore assembly by the membrane attack complex
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-019-10058-7
UR  - https://www.nature.com/articles/s41467-019-10058-7
UR  - http://hdl.handle.net/10044/1/70218
VL  - 10
ER  -
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