PMID: 12839991

 

    Legend: Sugar

Title : Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor Nogo-66 receptor and related proteins

Abstract :

1. The myelin-derived proteins Nogo , MAG and OMgp limit axonal regeneration after injury of the spinal cord and brain
2. These cell-surface proteins signal through multi- subunit neuronal receptors that contain a common ligand-binding glycosylphosphatidylinositol-anchored subunit termed the Nogo-66 receptor Nogo-66 receptor ( NgR )
3. By deletion analysis, we show that the binding of soluble fragments of Nogo , MAG and NgR to cell-surface NgR requires the entire leucine-rich repeat (LRR) region leucine-rich repeat (LRR) region of NgR , but not other portions of the protein
4. Despite sharing extensive sequence similarity with NgR , two related proteins , NgR2 and NgR3 , which we have identified, do not bind Nogo , MAG , OMgp or NgR
5. To investigate NgR specificity and multi-ligand binding, we determined the crystal structure of the biologically active ligand-binding soluble ectodomain of NgR
6. The molecule is banana shaped with elongation and curvature arising from eight LRRs flanked by an N-terminal cap and a small C-terminal subdomain
7. The NgR structure analysis, as well as a comparison of NgR surface residues not conserved in NgR2 and NgR3 , identifies potential protein interaction sites important in the assembly of a functional signaling complex