6pol

Crystal structure of the human NELL1 EGF1-3-Robo3 FN1 complex

spinqualitylabelsall models 6pol, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: CA, GOL, NAG, NO3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 affinity and is enhanced by ligand trimerization. Our results reveal a mechanism of oligomerization-induced Robo activation for axon guidance and shed light on Robo family member ligand binding specificity, conformational variability, divergent modes of signaling, and evolution. NELL2-Robo3 complex structure reveals mechanisms of receptor activation for axon guidance.,Pak JS, DeLoughery ZJ, Wang J, Acharya N, Park Y, Jaworski A, Ozkan E Nat Commun. 2020 Mar 20;11(1):1489. doi: 10.1038/s41467-020-15211-1. PMID:32198364 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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