Robo1 Forms a Compact Dimer-of-Dimers Assembly

Nataliia Aleksandrova; Irina Gutsche; Eaazhisai Kandiah; Sergiy Avilov; Maxim Petoukhov; Elena Seiradake; Andrew Mccarthy

doi:10.1016/j.str.2017.12.003

Article dans une revue

Robo1 Forms a Compact Dimer-of-Dimers Assembly

Nataliia Aleksandrova ¹ Irina Gutsche ² Eaazhisai Kandiah ² Sergiy Avilov ¹ Maxim Petoukhov ³ Elena Seiradake ⁴ Andrew Mccarthy ¹

1 EMBL - European Molecular Biology Laboratory [Grenoble]

2 IBS - UMR 5075 - Institut de biologie structurale

3 EMBL - European Molecular Biology Laboratory [Hamburg]

4 Department of Biochemistry [Oxford]

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.

Keywords : X-ray crystallography electron microscopy receptor robo slit

Type de document :

Article dans une revue

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire / Biologie structurale [q-bio.BM]

Liste complète des métadonnées

https://hal.univ-grenoble-alpes.fr/hal-01793858
Contributeur : Frank Thomas <>
Soumis le : jeudi 17 mai 2018 - 09:41:33
Dernière modification le : mardi 6 octobre 2020 - 16:12:03