2WV3

Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor

2WV3 の概要

• エントリーDOI: 10.2210/pdb2wv3/pdb
• 分子名称: NEUROPLASTIN, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: igcam, membrane, glycoprotein, cell membrane, cell adhesion, transmembrane, disulfide bond, alternative splicing, immunoglobulin domain
• 由来する生物種: RATTUS NORVEGICUS (RAT)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22027.53

構造登録者

Soroka, V.,Owczarek, S.,Kastrup, J.S.,Berezin, V.,Bock, E.,Gajhede, M. (登録日: 2009-10-13, 公開日: 2009-12-15, 最終更新日: 2024-10-23)

主引用文献

Owczarek, S.,Kiryushko, D.,Larsen, M.H.,Kastrup, J.S.,Gajhede, M.,Sandi, C.,Berezin, V.,Bock, E.,Soroka, V.
Neuroplastin-55 Binds to and Signals Through the Fibroblast Growth Factor Receptor
Faseb J., 24:1139-, 2010

PubMed Abstract: Neuroplastin (Np) is a glycoprotein belonging to the immunoglobulin superfamily of cell adhesion molecules (CAMs) and existing in two isoforms, Np55 and Np65, named according to their molecular weights. The extracellular part of Np65 contains three immunoglobulin (Ig)-like modules (Ig1, Ig2, and Ig3), whereas Np55 lacks the Ig1 module. Of these two isoforms, only Np65 is involved in homophilic interactions resulting in cell adhesion, whereas the role of Np55 is poorly understood. The present study reports for the first time the crystal structure of the ectodomain of Np55 at 1.95-A resolution and demonstrates that Np55 binds to and activates the fibroblast growth factor receptor 1 (FGFR1). Furthermore, we identify a sequence motif in the Ig2 module of Np55 interacting with FGFR1 and show that a synthetic peptide encompassing this motif, termed narpin, binds to and activates FGFR1. We show that both Np55 and the narpin peptide induce neurite outgrowth through FGFR1 activation and that Np55 increases synaptic calcium concentration in an FGFR1-dependent manner. Moreover, we demonstrate that narpin has an antidepressive-like effect in rats subjected to the forced swim test, suggesting that Np55-induced signaling may be involved in synaptic plasticity in vivo. Owczarek, S., Kiryushko, D., Larsen, M. H., Kastrup, J. S., Gajhede, M., Sandi, C., Berezin, V., Bock, E., Soroka, V. Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor.

PubMed: 19952283
DOI: 10.1096/FJ.09-140509

実験手法

X-RAY DIFFRACTION (1.95 Å)