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Structure. 2018 Feb 6;26(2):320-328.e4. doi: 10.1016/j.str.2017.12.003. Epub 2018 Jan 4.

Robo1 Forms a Compact Dimer-of-Dimers Assembly.

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European Molecular Biology Laboratory, Grenoble Outstation, 71 avenue des Martyrs, 38042 Grenoble, France.
University Grenoble Alpes, CNRS, CEA, IBS, 71 avenue des Martyrs, 38044 Grenoble, France.
European Molecular Biology Laboratory, Hamburg Unit, Notkestrasse 85, Hamburg 22607, Germany; Federal Scientific Research Centre "Crystallography and Photonics" of Russian Academy of Sciences, Leninsky Prospect 59, 119333 Moscow, Russian Federation; A. N. Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Leninsky Prospect 31, 119071 Moscow, Russian Federation; N.N. Semenov Institute of Chemical Physics of Russian Academy of Sciences, Kosygina Street 4, 119991 Moscow, Russian Federation.
Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UK.
European Molecular Biology Laboratory, Grenoble Outstation, 71 avenue des Martyrs, 38042 Grenoble, France. Electronic address:


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.


X-ray crystallography; electron microscopy; receptor; robo; slit

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