Related Experiment Video
Updated: Jan 28, 2026

Bringing the Visible Universe into Focus with Robo-AO
Published on: February 12, 2013
Structural Principles in Robo Activation and Auto-inhibition
Reut Barak1, Galit Yom-Tov1, Julia Guez-Haddad1
1The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Israel.
Abstract:
Proper brain function requires high-precision neuronal expansion and wiring, processes controlled by the transmembrane Roundabout (Robo) receptor family and their Slit ligands. Despite their great importance, the molecular mechanism by which Robos' switch from "off" to "on" states remains unclear. Here, we report a 3.6 Å crystal structure of the intact human Robo2 ectodomain (domains D1-8). We demonstrate that Robo cis dimerization via D4 is conserved through hRobo1, 2, and 3 and the C. elegans homolog SAX-3 and is essential for SAX-3 function in vivo. The structure reveals two levels of auto-inhibition that prevent premature activation: (1) cis blocking of the D4 dimerization interface and (2) trans interactions between opposing Robo receptors that fasten the D4-blocked conformation. Complementary experiments in mouse primary neurons and C. elegans support the auto-inhibition model. These results suggest that Slit stimulation primarily drives the release of Robo auto-inhibition required for dimerization and activation.
More Related Videos
10:24NMR-Based Activity Assays for Determining Compound Inhibition, IC50 Values, Artifactual Activity, and Whole-Cell Activity of Nucleoside Ribohydrolases
Published on: June 30, 2019
15:05Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
Related Concept Videos
Inhibition of Cdk Activity
Feedback Inhibition
The Uncertainty Principle
Hardy-Weinberg Principle
The Pauli Exclusion Principle
The Aufbau Principle and Hund's Rule