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Article dans une revue
Robo1 Forms a Compact Dimer-of-Dimers Assembly
Abstract : Roundabout (Robo) receptors provide an essential repulsive cue in neuronal development following Slit ligand binding. This important signaling pathway can also be hijacked in numerous cancers, making Slit-Robo an attractive therapeutic target. However, little is known about how Slit binding mediates Robo activation. Here we present the crystal structure of Robo1 Ig1-4 and Robo1 Ig5, together with a negative stain electron microscopy reconstruction of the Robo1 ectodomain. These results show how the Robo1 ectodomain is arranged as compact dimers, mainly mediated by the central Ig domains, which can further interact in a "back-to-back" fashion to generate a tetrameric assembly. We also observed no change in Robo1 oligomerization upon interaction with the dimeric Slit2-N ligand using fluorescent imaging. Taken together with previous studies we propose that Slit2-N binding results in a conformational change of Robo1 to trigger cell signaling.
https://hal.univ-grenoble-alpes.fr/hal-01793858
Contributeur : Frank Thomas <>
Soumis le : mardi 24 novembre 2020 - 09:45:44
Dernière modification le : lundi 29 mars 2021 - 14:41:00
Archivage à long terme le : : jeudi 25 février 2021 - 18:49:08
Contributeur : Frank Thomas <>
Soumis le : mardi 24 novembre 2020 - 09:45:44
Dernière modification le : lundi 29 mars 2021 - 14:41:00
Archivage à long terme le : : jeudi 25 février 2021 - 18:49:08
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Aleksandrova et al. Structure....
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