5o5i
Robo1 Ig5
Structural highlights
FunctionROBO1_HUMAN Receptor for SLIT1 and SLIT2 which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex. May be required for lung development.[1] Publication Abstract from PubMedRoundabout (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. Robo1 Forms a Compact Dimer-of-Dimers Assembly.,Aleksandrova N, Gutsche I, Kandiah E, Avilov SV, Petoukhov MV, Seiradake E, McCarthy AA Structure. 2017 Dec 28. pii: S0969-2126(17)30402-1. doi:, 10.1016/j.str.2017.12.003. PMID:29307485[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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