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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | rat megalin head | |||||||||
Map data | postprocess map | |||||||||
Sample |
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Keywords | endocytosis receptor / ENDOCYTOSIS | |||||||||
| Function / homology | Function and homology informationdiol metabolic process / positive regulation of oligodendrocyte progenitor proliferation / pulmonary artery morphogenesis / secondary heart field specification / folate import across plasma membrane / ventricular compact myocardium morphogenesis / response to leptin / metal ion transport / vitamin D metabolic process / cranial skeletal system development ...diol metabolic process / positive regulation of oligodendrocyte progenitor proliferation / pulmonary artery morphogenesis / secondary heart field specification / folate import across plasma membrane / ventricular compact myocardium morphogenesis / response to leptin / metal ion transport / vitamin D metabolic process / cranial skeletal system development / neuron projection arborization / coronary artery morphogenesis / outflow tract septum morphogenesis / aorta development / ventricular septum development / forebrain development / vagina development / endocytic vesicle / negative regulation of BMP signaling pathway / clathrin-coated pit / receptor-mediated endocytosis / neural tube closure / kidney development / phosphatidylinositol 3-kinase/protein kinase B signal transduction / brush border membrane / sensory perception of sound / male gonad development / protein transport / protein-folding chaperone binding / gene expression / cell population proliferation / receptor complex / endosome / apical plasma membrane / axon / external side of plasma membrane / dendrite / calcium ion binding / negative regulation of apoptotic process / endoplasmic reticulum / Golgi apparatus Similarity search - Function | |||||||||
| Biological species | ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.3 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: 2024Title: 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. | |||||||||
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Structure visualization
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_36692.map.gz | 5.4 MB | EMDB map data format | |
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| Header (meta data) | emd-36692-v30.xml emd-36692.xml | 25.3 KB 25.3 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_36692_fsc.xml | 9.2 KB | Display | FSC data file |
| Images | emd_36692.png | 192.3 KB | ||
| Masks | emd_36692_msk_1.map | 67 MB | Mask map | |
| Filedesc metadata | emd-36692.cif.gz | 9.3 KB | ||
| Others | emd_36692_half_map_1.map.gz emd_36692_half_map_2.map.gz | 40.9 MB 40.9 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36692 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36692 | HTTPS FTP |
-Validation report
| Summary document | emd_36692_validation.pdf.gz | 724.8 KB | Display | EMDB validaton report |
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| Full document | emd_36692_full_validation.pdf.gz | 724.4 KB | Display | |
| Data in XML | emd_36692_validation.xml.gz | 16.1 KB | Display | |
| Data in CIF | emd_36692_validation.cif.gz | 21.1 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36692 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36692 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8jx8MC ![]() 8jutC ![]() 8juuC ![]() 8jx9C ![]() 8jxaC ![]() 8jxbC ![]() 8jxcC ![]() 8jxdC ![]() 8jxeC ![]() 8jxfC ![]() 8jxgC ![]() 8jxhC ![]() 8jxiC ![]() 8jxjC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_36692.map.gz / Format: CCP4 / Size: 67 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | postprocess 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_36692_msk_1.map | ||||||||||||
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| Density Histograms |
-Half map: halfmap2
| File | emd_36692_half_map_1.map | ||||||||||||
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| Annotation | halfmap2 | ||||||||||||
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| Density Histograms |
-Half map: halmap1
| File | emd_36692_half_map_2.map | ||||||||||||
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| Annotation | halmap1 | ||||||||||||
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| Density Histograms |
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Sample components
+Entire : megalin dimer at pH7.4
+Supramolecule #1: megalin dimer at pH7.4
+Macromolecule #1: LDL receptor related protein 2
+Macromolecule #2: unclear peptide
+Macromolecule #3: unclear peptide
+Macromolecule #4: unclear peptide
+Macromolecule #5: unclear peptide
+Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #10: 2-acetamido-2-deoxy-alpha-D-galactopyranose
+Macromolecule #11: CALCIUM ION
+Macromolecule #12: NICKEL (II) ION
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 2.4 mg/mL |
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| Buffer | pH: 7.4 |
| Vitrification | Cryogen name: ETHANE |
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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 / Cs: 2.7 mm / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.8 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
| Initial model | Chain - Source name: AlphaFold / Chain - Initial model type: in silico model |
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| Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
| Output model | ![]() PDB-8jx8: |
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About Yorodumi




Keywords
Authors
Japan, 1 items
Citation







































Z (Sec.)
Y (Row.)
X (Col.)















































FIELD EMISSION GUN

