Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and related proteins Journal Article
| Authors: | Barton, W. A.; Liu, B. P.; Tzvetkova, D.; Jeffrey, P. D.; Fournier, A. E.; Sah, D.; Cate, R.; Strittmatter, S. M.; Nikolov, D. B. |
| Article Title: | Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and related proteins |
| Abstract: | The myelin-derived proteins Nogo, MAG and OMgp limit axonal regeneration after injury of the spinal cord and brain. These cell-surface proteins signal through multi-subunit neuronal receptors that contain a common ligand-binding glycosylphosphatidylinositol-anchored subunit termed the Nogo-66 receptor (NgR). 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 of NgR, but not other portions of the protein. 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. To investigate NgR specificity and multi-ligand binding, we determined the crystal structure of the biologically active ligand-binding soluble ectodomain of NgR. 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. 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. |
| Keywords: | signal transduction; controlled study; unclassified drug; human cell; gene deletion; nonhuman; protein conformation; animal cell; animals; mice; carboxy terminal sequence; embryo; brain injury; protein; protein binding; protein interaction; animalia; amino acid sequence; molecular sequence data; sequence homology, amino acid; amino terminal sequence; nucleotide sequence; binding site; crystal structure; models, molecular; receptor; protein structure; sequence homology; leucine; crystallization; ligand binding; nerve regeneration; axons; spinal cord injury; myelin; cell surface protein; receptors, cell surface; surface property; protein nogo; nerve fiber growth; axon outgrowth; glycosylphosphatidylinositol; receptor subunit; human; priority journal; article; myelin proteins; leucine-rich repeats; nogo-66 receptor; mag protein; ngr protein; ngr2 protein; ngr3 protein; nogo 66 receptor; omgp protein; leucine rich repeat |
| Journal Title: | EMBO Journal |
| Volume: | 22 |
| Issue: | 13 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2003-07-01 |
| Start Page: | 3291 |
| End Page: | 3302 |
| Language: | English |
| DOI: | 10.1093/emboj/cdg325 |
| PUBMED: | 12839991 |
| PROVIDER: | scopus |
| PMCID: | PMC165649 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Molecular Sequence Numbers: GENBANK: BK001302, BK001303, BK001304; -- Source: Scopus |
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