Robo1 forms a compact dimer-of-dimers assembly

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

Integrable Systems

Integrable systems which do not have an \u201cobvious\u201c group symmetry, beginning with the results of Poincar\ue9 and Bruns at the end of the last century, have been perceived as something exotic. The very insignificant list of such examples practically did not change until the 1960\u2019s. Although a number of fundamental methods of mathematical physics were based essentially on the perturbation-theory analysis of the simplest integrable examples, ideas about the structure of nontrivial integrable systems did not exert any real influence on the development of physics