Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Cryo-EM structures elucidate the multiligand receptor nature of megalin.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 121, Issue 22, Page e2318859121, Year 2024
Publish date	May 28, 2024
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 /
PubMed 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.
External links	Proc Natl Acad Sci U S A / PubMed:38771880 / PubMed Central
Methods	EM (single particle)
Resolution	3.2 - 4.2 Å
Structure data	36663 8jut EMDB-36663, PDB-8jut: rat megalin RAP complex Method: EM (single particle) / Resolution: 4.2 Å 36664 8juu EMDB-36664, PDB-8juu: rat megalin Method: EM (single particle) / Resolution: 3.8 Å 36692 8jx8 EMDB-36692, PDB-8jx8: rat megalin head Method: EM (single particle) / Resolution: 3.3 Å 36693 8jx9 EMDB-36693, PDB-8jx9: rat megalin bodyA Method: EM (single particle) / Resolution: 3.8 Å 36694 8jxa EMDB-36694, PDB-8jxa: cryo-EM structure of rat megalin bodyB Method: EM (single particle) / Resolution: 3.8 Å 36695 8jxb EMDB-36695: Cryo-EM structure of rat megalin wingA PDB-8jxb: Cryo-EM structure of rat megalin wingAc Method: EM (single particle) / Resolution: 3.7 Å 36696 8jxc EMDB-36696, PDB-8jxc: rat megalin wingB Method: EM (single particle) / Resolution: 3.7 Å 36697 8jxd EMDB-36697, PDB-8jxd: Cryo-EM structure of rat megalin leg Method: EM (single particle) / Resolution: 3.3 Å 36698 8jxe EMDB-36698, PDB-8jxe: rat megalin RAP complex head Method: EM (single particle) / Resolution: 3.2 Å 36699 8jxf EMDB-36699, PDB-8jxf: rat megalin RAP complex bodyA Method: EM (single particle) / Resolution: 3.6 Å 36700 8jxg EMDB-36700, PDB-8jxg: rat megalin RAP complex bodyB Method: EM (single particle) / Resolution: 3.2 Å 36701 8jxh EMDB-36701, PDB-8jxh: rat megalin RAP complex wingA Method: EM (single particle) / Resolution: 3.5 Å 36702 8jxi EMDB-36702, PDB-8jxi: rat megalin RAP complex wingB Method: EM (single particle) / Resolution: 3.4 Å 36703 8jxj EMDB-36703, PDB-8jxj: rat megalin RAP complex leg Method: EM (single particle) / Resolution: 3.9 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-A2G: 2-acetamido-2-deoxy-alpha-D-galactopyranose ChemComp-CA: Unknown entry ChemComp-NI: NICKEL (II) ION
Source	rattus norvegicus (Norway rat) Rattus (rat)
Keywords	ENDOCYTOSIS / endocytosis receptor