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Encarnação, J.C.* ; Napolitano, V.* ; Opassi, G.* ; Danielson, U.H.* ; Dubin, G.* ; Popowicz, G.M. ; Munier-Lehmann, H.* ; Buijs, J.* ; Andersson, K.* ; Björkelund, H.*

A real-time cell-binding assay reveals dynamic features of STxB-Gb3 cointernalization and STxB-mediated cargo delivery into cancer cells.

FEBS Lett. 594, 2406-2420 (2020)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
The interaction between the Shiga toxin B-subunit (STxB) and its globotriaosylceramide receptor (Gb3) has a high potential for being exploited for targeted cancer therapy. The primary goal of this study was to evaluate the capacity of STxB to carry small molecules and proteins as cargo into cells. For this purpose, an assay was designed to provide real-time information about the StxB-Gb3 interaction as well as the dynamics and mechanism of the internalization process. The assay revealed the ability to distinguish the process of binding to the cell surface from internalization and presented the importance of receptor and STxB clustering for internalization. The overall setup demonstrated that the binding mechanism is complex, and the concept of affinity is difficult to apply. Hence, time-resolved methods, providing detailed information about the interaction of STxB with cells, are critical for the optimization of intracellular delivery.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Binding Kinetics ; Cancer ; Cell Surface Receptor ; Real-time Cell-binding Assays ; Receptor Internalization ; Shiga Toxin; Toxin-b-subunit; Shiga Toxin; Kinetic-analysis; Living Cells; Receptor; Surface; Temperature; Molecules; Impact; Golgi
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 0014-5793
e-ISSN 1873-3468
Zeitschrift FEBS Letters
Quellenangaben Band: 594, Heft: 15, Seiten: 2406-2420 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503000-001
DOI 10.1002/1873-3468.13847
WOS ID WOS:000541910100001
Scopus ID 85087211369
PubMed ID 32473599
Erfassungsdatum 2020-06-02
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