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Issue 23, 2016
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Membrane invagination induced by Shiga toxin B-subunit: from molecular structure to tube formation

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Abstract

The bacterial Shiga toxin is composed of an enzymatically active A-subunit, and a receptor-binding homopentameric B-subunit (STxB) that mediates intracellular toxin trafficking. Upon STxB-mediated binding to the glycolipid globotriaosylceramide (Gb3) at the plasma membrane of target cells, Shiga toxin is internalized by clathrin-dependent and independent endocytosis. The formation of tubular membrane invaginations is an essential step in the clathrin-independent STxB uptake process. However, the mechanism by which STxB induces these invaginations has remained unclear. Using a combination of all-atom molecular dynamics and Monte Carlo simulations we show that the molecular architecture of STxB enables the following sequence of events: the Gb3 binding sites on STxB are arranged such that tight avidity-based binding results in a small increment of local curvature. Membrane-mediated clustering of several toxin molecules then creates a tubular membrane invagination that drives toxin entry into the cell. This mechanism requires: (1) a precise molecular architecture of the STxB binding sites; (2) a fluid bilayer in order for the tubular invagination to form. Although, STxB binding to the membrane requires specific interactions with Gb3 lipids, our study points to a generic molecular design principle for clathrin-independent endocytosis of nanoparticles.

Graphical abstract: Membrane invagination induced by Shiga toxin B-subunit: from molecular structure to tube formation

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Publication details

The article was received on 22 Feb 2016, accepted on 06 Apr 2016 and first published on 06 Apr 2016


Article type: Paper
DOI: 10.1039/C6SM00464D
Soft Matter, 2016,12, 5164-5171
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    Membrane invagination induced by Shiga toxin B-subunit: from molecular structure to tube formation

    W. Pezeshkian, A. G. Hansen, L. Johannes, H. Khandelia, J. C. Shillcock, P. B. S. Kumar and J. H. Ipsen, Soft Matter, 2016, 12, 5164
    DOI: 10.1039/C6SM00464D

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