5LF5

Myelin-associated glycoprotein (MAG) deglycosylated full extracellular domain with co-purified ligand

5LF5 の概要

• エントリーDOI: 10.2210/pdb5lf5/pdb
• 分子名称: Myelin-associated glycoprotein, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose, ... (5 entities in total)
• 機能のキーワード: myelin, cell adhesion, signaling
• 由来する生物種: Mus musculus (House Mouse)
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein : P20917
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57299.93

構造登録者

Pronker, M.F.,Janssen, B.J.C. (登録日: 2016-06-30, 公開日: 2016-12-14, 最終更新日: 2024-10-23)

主引用文献

Pronker, M.F.,Lemstra, S.,Snijder, J.,Heck, A.J.,Thies-Weesie, D.M.,Pasterkamp, R.J.,Janssen, B.J.
Structural basis of myelin-associated glycoprotein adhesion and signalling.
Nat Commun, 7:13584-13584, 2016

PubMed Abstract: Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. The mechanisms underlying MAG adhesion and signalling are unresolved. We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1. Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling.

PubMed: 27922006
DOI: 10.1038/ncomms13584

実験手法

X-RAY DIFFRACTION (3.8 Å)