EMD-28233

Single-particle
2.83 Å
EMD-28233 Deposition: 26/09/2022
Map released: 08/02/2023
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-28233

Cryo-EM structure of LRP2 at pH 7.5

EMD-28233

Single-particle
2.83 Å
EMD-28233 Deposition: 26/09/2022
Map released: 08/02/2023
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Mus musculus
Sample: LRP2 at neutral pH
Fitted models: 8em4 (Avg. Q-score: 0.36)

Deposition Authors: Beenken A , Cerutti G , Brasch J, Fitzpatrick AW , Barasch J , Shapiro L
Structures of LRP2 reveal a molecular machine for endocytosis.
PUBMED: 36750096
DOI: doi:10.1016/j.cell.2023.01.016
ISSN: 1097-4172
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.