Evidence map›Paper›PMID 31061395›Full record

ArticleNature communications2019

Single-molecule kinetics of pore assembly by the membrane attack complex.

Edward S Parsons, George J Stanley, Alice L B Pyne, Adrian W Hodel, Adrian P Nievergelt, Anaïs Menny, Alexander R Yon, Ashlea Rowley, Ralf P Richter, Georg E Fantner and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Edward S ParsonsLondon Centre for Nanotechnology, University College London, London, WC1H 0AH, UK. e.parsons@ucl.ac.uk.
George J StanleyLondon Centre for Nanotechnology, University College London, London, WC1H 0AH, UK.
Alice L B PyneLondon Centre for Nanotechnology, University College London, London, WC1H 0AH, UK.ORCID http://orcid.org/0000-0002-2658-8987
Adrian W HodelLondon Centre for Nanotechnology, University College London, London, WC1H 0AH, UK.
Adrian P NievergeltLaboratory for Bio- and Nano-Instrumentation, Swiss Federal Institute of Technology Lausanne (EPFL), 1015, Lausanne, Switzerland.ORCID http://orcid.org/0000-0003-3772-6318
Anaïs MennyDepartment of Life Sciences, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Alexander R YonLondon Centre for Nanotechnology, University College London, London, WC1H 0AH, UK.
Ashlea RowleySchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
Ralf P RichterSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
Georg E FantnerLaboratory for Bio- and Nano-Instrumentation, Swiss Federal Institute of Technology Lausanne (EPFL), 1015, Lausanne, Switzerland.ORCID http://orcid.org/0000-0001-5889-3022
Doryen BubeckDepartment of Life Sciences, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.ORCID http://orcid.org/0000-0001-8241-9697
Bart W HoogenboomLondon Centre for Nanotechnology, University College London, London, WC1H 0AH, UK. b.hoogenboom@ucl.ac.uk.ORCID http://orcid.org/0000-0002-8882-4324

Funding

Cancer Research UK 16099Medical Research Council MR/R000328/1Medical Research Council MR/R024871/1Medical Research Council MR/R024871/2
6 · The paper itself

Abstract

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.

Indexed as

Protein MultimerizationCD59 AntigensCell MembraneComplement C5Complement C8Complement C9Complement Membrane Attack ComplexHumansKineticsMicroscopy, Atomic ForceSingle Molecule ImagingCD59 AntigensCD59 protein, humanComplement C5complement C5b-7 complexComplement C8Complement C9Complement Membrane Attack Complex

Identifiers

PMID31061395
PMCPMC6502846

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.