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NELL2-Robo3 complex structure reveals mechanisms of receptor activation for axon guidance

Nat Commun. 2020; 
Pak JS, DeLoughery ZJ, Wang J, Acharya N, Park Y, Jaworski A, Özkan E, .
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Catalog Antibody 1% Bovine Serum Albumin), incubated with an iFluor488-coupled anti-FLAG antibody (GenScript, 1 µg/ml) for 30 min at 4 °C and washed with PBSB twice.... Quantitation of purified protein from SEC and secreted protein in conditioned media for ECIA was achieved using western blots against the hexahistidine epitope present at the C-termini of all constructs (anti- body: fluorescent His-Tag Antibody with iFluor 488, Genscript, catalog no. Get A Quote

摘要

Axon pathfinding is critical for nervous system development, and it is orchestrated by molecular cues that activate receptors on the axonal growth cone. Robo family receptors bind Slit guidance cues to mediate axon repulsion. In mammals, the divergent family member Robo3 does not bind Slits, but instead signals axon repulsion from its own ligand, NELL2. Conversely, canonical Robos do not mediate NELL2 signaling. Here, we present the structures of NELL-Robo3 complexes, identifying a mode of ligand engagement for Robos that is orthogonal to Slit binding. We elucidate the structural basis for differential binding between NELL and Robo family members and show that NELL2 repulsive activity is a function of its Robo3... More

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