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Real-time visualization of perforin nanopore assembly

Leung, C; Hodel, AW; Brennan, AJ; Lukoyanova, N; Tran, S; House, CM; Kondos, SC; ... Hoogenboom, BW; + view all (2017) Real-time visualization of perforin nanopore assembly. Nature Nanotechnology , 12 pp. 467-473. 10.1038/nnano.2016.303. Green open access

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Abstract

Perforin is a key protein of the vertebrate immune system. Secreted by cytotoxic lymphocytes as soluble monomers, perforin can self-assemble into oligomeric pores of 10-20 nm inner diameter in the membranes of virus-infected and cancerous cells. These large pores facilitate the entry of pro-apoptopic granzymes, thereby rapidly killing the target cell. To elucidate the pathways of perforin pore assembly, we carried out real-time atomic force microscopy and electron microscopy studies. Our experiments reveal that the pore assembly proceeds via a membrane-bound prepore intermediate state, typically consisting of up to approximately eight loosely but irreversibly assembled monomeric subunits. These short oligomers convert to more closely packed membrane nanopore assemblies, which can subsequently recruit additional prepore oligomers to grow the pore size.

Type: Article
Title: Real-time visualization of perforin nanopore assembly
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nnano.2016.303
Publisher version: http://dx.doi.org/10.1038/nnano.2016.303
Language: English
Additional information: Copyright © 2017, Rights Managed by Nature Publishing Group.
Keywords: Applications of AFM, Nanopores
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
URI: https://discovery.ucl.ac.uk/id/eprint/1540325
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