Robo1 Forms a Compact Dimer-of-Dimers Assemblyстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 10 августа 2018 г.
Аннотация: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.