- EMDB-28233: Cryo-EM structure of LRP2 at pH 7.5 -
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基本情報
登録情報
データベース: EMDB / ID: EMD-28233
タイトル
Cryo-EM structure of LRP2 at pH 7.5
マップデータ
試料
複合体: LRP2 at neutral pH
タンパク質・ペプチド: Low-density lipoprotein receptor-related protein 2
リガンド: 2-acetamido-2-deoxy-beta-D-galactopyranose
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
リガンド: CALCIUM ION
キーワード
LRP2 / Megalin / GP330 / Endocytosis / MEMBRANE PROTEIN
機能・相同性
機能・相同性情報
Transport of RCbl within the body / diol metabolic process / positive regulation of oligodendrocyte progenitor proliferation / pulmonary artery morphogenesis / secondary heart field specification / Retinoid metabolism and transport / folate import across plasma membrane / ventricular compact myocardium morphogenesis / response to leptin / metal ion transport ...Transport of RCbl within the body / diol metabolic process / positive regulation of oligodendrocyte progenitor proliferation / pulmonary artery morphogenesis / secondary heart field specification / Retinoid metabolism and transport / folate import across plasma membrane / ventricular compact myocardium morphogenesis / response to leptin / metal ion transport / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / vitamin D metabolic process / cranial skeletal system development / neuron projection arborization / coronary artery morphogenesis / outflow tract septum morphogenesis / coronary vasculature development / positive regulation of neurogenesis / aorta development / ventricular septum development / vagina development / outflow tract morphogenesis / brush border / endocytic vesicle / negative regulation of BMP signaling pathway / forebrain development / clathrin-coated pit / receptor-mediated endocytosis / endosome lumen / kidney development / neural tube closure / phosphatidylinositol 3-kinase/protein kinase B signal transduction / brush border membrane / sensory perception of sound / SH3 domain binding / male gonad development / apical part of cell / protein transport / protein-folding chaperone binding / heart development / gene expression / cell population proliferation / receptor complex / endosome / apical plasma membrane / external side of plasma membrane / axon / dendrite / calcium ion binding / negative regulation of apoptotic process / endoplasmic reticulum / Golgi apparatus / membrane / plasma membrane 類似検索 - 分子機能
LRP2-like, EGF-like domain / Complement Clr-like EGF domain / Complement Clr-like EGF-like / : / Low-density lipoprotein receptor repeat class B / LDL-receptor class B (LDLRB) repeat profile. / LDLR class B repeat / Low-density lipoprotein-receptor YWTD domain / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A, conserved site ...LRP2-like, EGF-like domain / Complement Clr-like EGF domain / Complement Clr-like EGF-like / : / Low-density lipoprotein receptor repeat class B / LDL-receptor class B (LDLRB) repeat profile. / LDLR class B repeat / Low-density lipoprotein-receptor YWTD domain / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A, conserved site / : / LDL-receptor class A (LDLRA) domain signature. / Calcium-binding EGF domain / LDL-receptor class A (LDLRA) domain profile. / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A repeat / LDL receptor-like superfamily / Six-bladed beta-propeller, TolB-like / Coagulation Factor Xa inhibitory site / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / Epidermal growth factor-like domain. / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 1. / EGF-like domain signature 2. / EGF-like domain 類似検索 - ドメイン・相同性
Low-density lipoprotein receptor-related protein 2 類似検索 - 構成要素
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
DK124667
米国
引用
ジャーナル: Cell / 年: 2023 タイトル: Structures of LRP2 reveal a molecular machine for endocytosis. 著者: Andrew Beenken / Gabriele Cerutti / Julia Brasch / Yicheng Guo / Zizhang Sheng / Hediye Erdjument-Bromage / Zainab Aziz / Shelief Y Robbins-Juarez / Estefania Y Chavez / Goran Ahlsen / ...著者: Andrew Beenken / Gabriele Cerutti / Julia Brasch / Yicheng Guo / Zizhang Sheng / Hediye Erdjument-Bromage / Zainab Aziz / Shelief Y Robbins-Juarez / Estefania Y Chavez / Goran Ahlsen / Phinikoula S Katsamba / Thomas A Neubert / Anthony W P Fitzpatrick / Jonathan Barasch / Lawrence Shapiro / 要旨: The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in ...The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in endocytosis and are implicated in diseases of the kidney and brain. Here, we report high-resolution cryoelectron microscopy structures of LRP2 isolated from mouse kidney, at extracellular and endosomal pH. The structures reveal LRP2 to be a molecular machine that adopts a conformation for ligand binding at the cell surface and for ligand shedding in the endosome. LRP2 forms a homodimer, the conformational transformation of which is governed by pH-sensitive sites at both homodimer and intra-protomer interfaces. A subset of LRP2 deleterious missense variants in humans appears to impair homodimer assembly. These observations lay the foundation for further understanding the function and mechanism of LDL receptors and implicate homodimerization as a conserved feature of the LRP receptor subfamily.