+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36663 | |||||||||
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Title | rat megalin RAP complex | |||||||||
Map data | postprocess consensus map | |||||||||
Sample |
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Keywords | endocytosis receptor / ENDOCYTOSIS | |||||||||
Function / homology | Function and homology information lipase binding / negative regulation of very-low-density lipoprotein particle clearance / regulation of receptor-mediated endocytosis / rough endoplasmic reticulum lumen / receptor antagonist activity / amyloid-beta clearance by transcytosis / negative regulation of amyloid-beta clearance / very-low-density lipoprotein particle receptor binding / cis-Golgi network / negative regulation of receptor internalization ...lipase binding / negative regulation of very-low-density lipoprotein particle clearance / regulation of receptor-mediated endocytosis / rough endoplasmic reticulum lumen / receptor antagonist activity / amyloid-beta clearance by transcytosis / negative regulation of amyloid-beta clearance / very-low-density lipoprotein particle receptor binding / cis-Golgi network / negative regulation of receptor internalization / low-density lipoprotein particle receptor binding / endoplasmic reticulum-Golgi intermediate compartment / endomembrane system / endosome lumen / Golgi lumen / endocytosis / heparin binding / vesicle / endosome / receptor ligand activity / calcium ion binding / Golgi apparatus / cell surface / signal transduction / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | Goto S / Tsutsumi A / Lee Y / Hosojima M / Kabasawa H / Komochi K / Yun-san L / Nagatoshi S / Tsumoto K / Nishizawa T ...Goto S / Tsutsumi A / Lee Y / Hosojima M / Kabasawa H / Komochi K / Yun-san L / Nagatoshi S / Tsumoto K / Nishizawa T / Kikkawa M / Saito A | |||||||||
Funding support | Japan, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2024 Title: Cryo-EM structures elucidate the multiligand receptor nature of megalin. Authors: Sawako Goto / Akihisa Tsutsumi / Yongchan Lee / Michihiro Hosojima / Hideyuki Kabasawa / Koichi Komochi / Satoru Nagatoishi / Kazuya Takemoto / Kouhei Tsumoto / Tomohiro Nishizawa / Masahide ...Authors: Sawako Goto / Akihisa Tsutsumi / Yongchan Lee / Michihiro Hosojima / Hideyuki Kabasawa / Koichi Komochi / Satoru Nagatoishi / Kazuya Takemoto / Kouhei Tsumoto / Tomohiro Nishizawa / Masahide Kikkawa / Akihiko Saito / Abstract: Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and ...Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. Saito, , 106393 (2023)]. It is expressed predominantly in renal proximal tubule epithelial cells, as well as in the brain, lungs, eyes, inner ear, thyroid gland, and placenta. Megalin is also known to mediate the endocytosis of toxic compounds, particularly those that cause renal and hearing disorders [Y. Hori , , 1783-1791 (2017)]. Genetic megalin deficiency causes Donnai-Barrow syndrome/facio-oculo-acoustico-renal syndrome in humans. However, it is not known how megalin interacts with such a wide variety of ligands and plays pathological roles in various organs. In this study, we elucidated the dimeric architecture of megalin, purified from rat kidneys, using cryoelectron microscopy. The maps revealed the densities of endogenous ligands bound to various regions throughout the dimer, elucidating the multiligand receptor nature of megalin. We also determined the structure of megalin in complex with receptor-associated protein, a molecular chaperone for megalin. The results will facilitate further studies on the pathophysiology of megalin-dependent multiligand endocytic pathways in multiple organs and will also be useful for the development of megalin-targeted drugs for renal and hearing disorders, Alzheimer's disease [B. V. Zlokovic , , 4229-4234 (1996)], and other illnesses. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36663.map.gz | 42.8 MB | EMDB map data format | |
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Header (meta data) | emd-36663-v30.xml emd-36663.xml | 30.7 KB 30.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36663_fsc.xml | 9.2 KB | Display | FSC data file |
Images | emd_36663.png | 169.4 KB | ||
Masks | emd_36663_msk_1.map | 67 MB | Mask map | |
Filedesc metadata | emd-36663.cif.gz | 9.8 KB | ||
Others | emd_36663_additional_1.map.gz emd_36663_half_map_1.map.gz emd_36663_half_map_2.map.gz | 28.6 MB 52.2 MB 52.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36663 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36663 | HTTPS FTP |
-Validation report
Summary document | emd_36663_validation.pdf.gz | 955.5 KB | Display | EMDB validaton report |
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Full document | emd_36663_full_validation.pdf.gz | 955.1 KB | Display | |
Data in XML | emd_36663_validation.xml.gz | 16.1 KB | Display | |
Data in CIF | emd_36663_validation.cif.gz | 21 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36663 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36663 | HTTPS FTP |
-Related structure data
Related structure data | 8jutMC 8juuC 8jx8C 8jx9C 8jxaC 8jxbC 8jxcC 8jxdC 8jxeC 8jxfC 8jxgC 8jxhC 8jxiC 8jxjC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_36663.map.gz / Format: CCP4 / Size: 67 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | postprocess consensus map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.411 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_36663_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: composite map
File | emd_36663_additional_1.map | ||||||||||||
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Annotation | composite map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: halfmap1
File | emd_36663_half_map_1.map | ||||||||||||
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Annotation | halfmap1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: halfmap2
File | emd_36663_half_map_2.map | ||||||||||||
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Annotation | halfmap2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : megalin-RAP complex
+Supramolecule #1: megalin-RAP complex
+Macromolecule #1: LDL receptor related protein 2
+Macromolecule #2: Alpha-2-macroglobulin receptor-associated protein
+Macromolecule #3: unclear peptide
+Macromolecule #4: unclear peptide
+Macromolecule #5: unclear peptide
+Macromolecule #6: unclear peptide
+Macromolecule #7: unclear peptide
+Macromolecule #8: unclear peptide
+Macromolecule #17: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #18: 2-acetamido-2-deoxy-alpha-D-galactopyranose
+Macromolecule #19: CALCIUM ION
+Macromolecule #20: NICKEL (II) ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.6 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |