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Open data
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Basic information
Entry | Database: PDB / ID: 8jxh | ||||||
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Title | rat megalin RAP complex wingA | ||||||
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![]() | ENDOCYTOSIS / endocytosis receptor | ||||||
Function / homology | ![]() 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 / hormone binding / very-low-density lipoprotein particle receptor binding / cis-Golgi network ...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 / hormone binding / 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 / receptor-mediated endocytosis / endosome lumen / Golgi lumen / heparin binding / vesicle / receptor ligand activity / receptor complex / endosome / apical plasma membrane / calcium ion binding / Golgi apparatus / cell surface / signal transduction / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 443.7 KB | Display | ![]() |
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PDB format | ![]() | 277.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 54.9 KB | Display | |
Data in CIF | ![]() | 81.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 36701MC ![]() 8jutC ![]() 8juuC ![]() 8jx8C ![]() 8jx9C ![]() 8jxaC ![]() 8jxbC ![]() 8jxcC ![]() 8jxdC ![]() 8jxeC ![]() 8jxfC ![]() 8jxgC ![]() 8jxiC ![]() 8jxjC C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 2 types, 3 molecules DAB
#1: Protein | Mass: 38908.754 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#2: Protein | Mass: 519871.438 Da / Num. of mol.: 2 / Source method: isolated from a natural source Details: Authors could not experimentally confirm this sequence, but the sequence should be a part of molecule 2. Therefore the residue numbers and chain IDs are meaningless for molecule 3 and 4. Source: (natural) ![]() ![]() |
-Protein/peptide , 2 types, 2 molecules QR
#3: Protein/peptide | Mass: 528.644 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#4: Protein/peptide | Mass: 472.537 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Sugars , 5 types, 17 molecules ![](data/chem/img/NAG.gif)
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#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #7: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #8: Sugar | ChemComp-NAG / #9: Sugar | ChemComp-A2G / |
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-Non-polymers , 1 types, 16 molecules ![](data/chem/img/CA.gif)
#10: Chemical | ChemComp-CA / |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 600 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 67775 / Algorithm: BACK PROJECTION / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Source name: AlphaFold / Type: in silico model |