8JUT

rat megalin RAP complex

8JUT の概要

• エントリーDOI: 10.2210/pdb8jut/pdb
• EMDBエントリー: 36663
• 分子名称: LDL receptor related protein 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, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (20 entities in total)
• 機能のキーワード: endocytosis receptor, endocytosis
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 1172517.87

構造登録者

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. (登録日: 2023-06-27, 公開日: 2024-06-19, 最終更新日: 2024-11-06)

主引用文献

Goto, S.,Tsutsumi, A.,Lee, Y.,Hosojima, M.,Kabasawa, H.,Komochi, K.,Nagatoishi, S.,Takemoto, K.,Tsumoto, K.,Nishizawa, T.,Kikkawa, M.,Saito, A.
Cryo-EM structures elucidate the multiligand receptor nature of megalin.
Proc.Natl.Acad.Sci.USA, 121:e2318859121-e2318859121, 2024

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 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.

PubMed: 38771880
DOI: 10.1073/pnas.2318859121

実験手法

ELECTRON MICROSCOPY (4.2 Å)