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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | rat megalin | |||||||||
![]() | postprocess map | |||||||||
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![]() | endocytosis receptor / ENDOCYTOSIS | |||||||||
Function / homology | ![]() hormone binding / receptor-mediated endocytosis / receptor complex / apical plasma membrane / calcium ion binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | 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 | ![]()
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![]() | ![]() 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. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
Map data | ![]() | 9.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 29.9 KB 29.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.2 KB | Display | ![]() |
Images | ![]() | 175.8 KB | ||
Masks | ![]() | 67 MB | ![]() | |
Filedesc metadata | ![]() | 9.5 KB | ||
Others | ![]() ![]() ![]() | 28.4 MB 52.2 MB 52.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8juuMC ![]() 8jutC ![]() 8jx8C ![]() 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 ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | postprocess map | ||||||||||||||||||||
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
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-Additional map: #1
File | emd_36664_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: halfmap1
File | emd_36664_half_map_1.map | ||||||||||||
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Annotation | halfmap1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: halfmap2
File | emd_36664_half_map_2.map | ||||||||||||
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Annotation | halfmap2 | ||||||||||||
Projections & Slices |
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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 #6: unclear peptide
+Macromolecule #7: unclear peptide
+Macromolecule #12: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #13: 2-acetamido-2-deoxy-alpha-D-galactopyranose
+Macromolecule #14: CALCIUM ION
+Macromolecule #15: NICKEL (II) ION
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | 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: ![]() |
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 |
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Refinement | Space: REAL / Protocol: RIGID BODY FIT |
Output model | ![]() PDB-8juu: |