8EM7

Cryo-EM structure of LRP2 at pH 5.2

8EM7 の概要

• エントリーDOI: 10.2210/pdb8em7/pdb
• EMDBエントリー: 28233 28241 28242 28243 28250
• 分子名称: Low-density lipoprotein receptor-related protein 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: lrp2, megalin, gp330, endocytosis, membrane protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 1070856.04

構造登録者

Beenken, A.,Cerutti, G.,Fitzpatrick, A.W.,Barasch, J.,Shapiro, L. (登録日: 2022-09-27, 公開日: 2023-02-08, 最終更新日: 2023-03-08)

主引用文献

Beenken, A.,Cerutti, G.,Brasch, J.,Guo, Y.,Sheng, Z.,Erdjument-Bromage, H.,Aziz, Z.,Robbins-Juarez, S.Y.,Chavez, E.Y.,Ahlsen, G.,Katsamba, P.S.,Neubert, T.A.,Fitzpatrick, A.W.P.,Barasch, J.,Shapiro, L.
Structures of LRP2 reveal a molecular machine for endocytosis.
Cell, 186:821-, 2023

PubMed Abstract: The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in endocytosis and are implicated in diseases of the kidney and brain. Here, we report high-resolution cryoelectron microscopy structures of LRP2 isolated from mouse kidney, at extracellular and endosomal pH. The structures reveal LRP2 to be a molecular machine that adopts a conformation for ligand binding at the cell surface and for ligand shedding in the endosome. LRP2 forms a homodimer, the conformational transformation of which is governed by pH-sensitive sites at both homodimer and intra-protomer interfaces. A subset of LRP2 deleterious missense variants in humans appears to impair homodimer assembly. These observations lay the foundation for further understanding the function and mechanism of LDL receptors and implicate homodimerization as a conserved feature of the LRP receptor subfamily.

PubMed: 36750096
DOI: 10.1016/j.cell.2023.01.016

実験手法

ELECTRON MICROSCOPY (2.97 Å)