4Q4B

Crystal structure of LIMP-2 (space group C2221)

4Q4B の概要

• エントリーDOI: 10.2210/pdb4q4b/pdb
• 関連するPDBエントリー: 4Q4F
• 分子名称: Lysosome membrane protein 2, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: lysosomal targeting, beta-glucocerebrosidase, ci-mpr, er, endosome, lysosome, cell adhesion
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Lysosome membrane; Multi-pass membrane protein: Q14108
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53194.66

構造登録者

Zhao, Y.,Ren, J.,Padilla-Parra, S.,Fry, L.E.,Stuart, D.I. (登録日: 2014-04-14, 公開日: 2014-07-30, 最終更新日: 2023-09-20)

主引用文献

Zhao, Y.,Ren, J.,Padilla-Parra, S.,Fry, E.E.,Stuart, D.I.
Lysosome sorting of beta-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor.
Nat Commun, 5:4321-4321, 2014

PubMed Abstract: The integral membrane protein LIMP-2 has been a paradigm for mannose 6-phosphate receptor (MPR) independent lysosomal targeting, binding to β-glucocerebrosidase (β-GCase) and directing it to the lysosome, before dissociating in the late-endosomal/lysosomal compartments. Here we report structural results illuminating how LIMP-2 binds and releases β-GCase according to changes in pH, via a histidine trigger, and suggesting that LIMP-2 localizes the ceramide portion of the substrate adjacent to the β-GCase catalytic site. Remarkably, we find that LIMP-2 bears P-Man9GlcNAc2 covalently attached to residue N325, and that it binds MPR, via mannose 6-phosphate, with a similar affinity to that observed between LIMP-2 and β-GCase. The binding sites for β-GCase and the MPR are functionally separate, so that a stable ternary complex can be formed. By fluorescence lifetime imaging microscopy, we also demonstrate that LIMP-2 interacts with MPR in living cells. These results revise the accepted view of LIMP-2-β-GCase lysosomal targeting.

PubMed: 25027712
DOI: 10.1038/ncomms5321

実験手法

X-RAY DIFFRACTION (2.82 Å)