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Reference: Gilbert, RJ and Sonnen, AF-P, (2016). Measuring kinetic drivers of pneumolysin pore structure. European Biophysics Journal, 45 (4), 365-376.Citable link to this page:


Measuring kinetic drivers of pneumolysin pore structure.

Abstract: Most membrane attack complex-perforin/cholesterol-dependent cytolysin (MACPF/CDC) proteins are thought to form pores in target membranes by assembling into pre-pore oligomers before undergoing a pre-pore to pore transition. Assembly during pore formation is into both full rings of subunits and incomplete rings (arcs). The balance between arcs and full rings is determined by a mechanism dependent on protein concentration in which arc pores arise due to kinetic trapping of the pre-pore forms by the depletion of free protein subunits during oligomerisation. Here we describe the use of a kinetic assay to study pore formation in red blood cells by the MACPF/CDC pneumolysin from Streptococcus pneumoniae. We show that cell lysis displays two kinds of dependence on protein concentration. At lower concentrations it is dependent on the pre-pore topore transition of arc oligomers, which we show to be a cooperative process. At higher concentrations it is dependent on the amount of pneumolysin bound to the membrane and reflects the affinity of the protein for its receptor, cholesterol. A lag occurs before cell lysis begins; this is dependent on oligomerisation of pneumolysin. Kinetic dissection of cell lysis by pneumolysin demonstrates the capacity of MACPF/CDCs to generate pore-forming oligomericstructures of variable size with, most likely, different functional roles in biology.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Accepted manuscript Funder: Wellcome Trust   Notes:© The Author(s) 2016 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Bibliographic Details

Publisher: Springer

Publisher Website:

Journal: European Biophysics Journalsee more from them

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Issue Date: 2016-02


Urn: uuid:ae4c124f-991d-45cb-a526-ffe03958a0f6

Source identifier: 609496

Eissn: 1432-1017


Issn: 0175-7571 Item Description

Type: Journal article;

Language: eng

Version: Accepted manuscriptKeywords: pore formation kinetics MACPF/CDC toroidal pore oligomerisation membrane structure Tiny URL: pubs:609496


Autor: Gilbert, RJ - institutionUniversity of Oxford Oxford, MSD, NDM, Structural Biology - - - Sonnen, AF-P - - - - Bibliographic Detai



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