+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8em7 | ||||||
---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of LRP2 at pH 5.2 | ||||||
要素 | Low-density lipoprotein receptor-related protein 2 | ||||||
キーワード | MEMBRANE PROTEIN / LRP2 / Megalin / GP330 / Endocytosis | ||||||
機能・相同性 | 機能・相同性情報 Transport of RCbl within the body / endocytic hemoglobin import into cell / diol metabolic process / chemoattraction of axon / positive regulation of lipoprotein transport / pulmonary artery morphogenesis / secondary heart field specification / Retinoid metabolism and transport / positive regulation of oligodendrocyte progenitor proliferation / folate import across plasma membrane ...Transport of RCbl within the body / endocytic hemoglobin import into cell / diol metabolic process / chemoattraction of axon / positive regulation of lipoprotein transport / pulmonary artery morphogenesis / secondary heart field specification / Retinoid metabolism and transport / positive regulation of oligodendrocyte progenitor proliferation / folate import across plasma membrane / ventricular compact myocardium morphogenesis / response to leptin / metal ion transport / protein transporter activity / hormone binding / Cargo recognition for clathrin-mediated endocytosis / vitamin D metabolic process / neuron projection arborization / Clathrin-mediated endocytosis / hormone secretion / coronary artery morphogenesis / outflow tract septum morphogenesis / coronary vasculature development / insulin-like growth factor I binding / transcytosis / protein import / aorta development / cargo receptor activity / ventricular septum development / positive regulation of neurogenesis / endosomal transport / low-density lipoprotein particle receptor binding / hemoglobin binding / amyloid-beta clearance / positive regulation of endocytosis / brush border / vagina development / endocytic vesicle / negative regulation of BMP signaling pathway / response to X-ray / axonal growth cone / clathrin-coated pit / forebrain development / receptor-mediated endocytosis / kidney development / neural tube closure / endosome lumen / nuclear receptor binding / PDZ domain binding / brush border membrane / sensory perception of sound / cellular response to growth factor stimulus / SH3 domain binding / endocytosis / male gonad development / protein transport / apical part of cell / heart development / protein-folding chaperone binding / cell population proliferation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / endosome / apical plasma membrane / membrane raft / external side of plasma membrane / axon / dendrite / calcium ion binding / protein-containing complex binding / negative regulation of apoptotic process / Golgi apparatus / cell surface / endoplasmic reticulum / protein-containing complex / extracellular space / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | Mus musculus (ハツカネズミ) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.97 Å | ||||||
データ登録者 | Beenken, A. / Cerutti, G. / Fitzpatrick, A.W. / Barasch, J. / Shapiro, L. | ||||||
資金援助 | 米国, 1件
| ||||||
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. | ||||||
履歴 |
|
-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
---|
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8em7.cif.gz | 1.5 MB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb8em7.ent.gz | 1.2 MB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8em7.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/em/8em7 ftp://data.pdbj.org/pub/pdb/validation_reports/em/8em7 | HTTPS FTP |
---|
-関連構造データ
関連構造データ | 28241MC 8em4C M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
#1: タンパク質 | 分子量: 519746.500 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Mus musculus (ハツカネズミ) / 参照: UniProt: A2ARV4 #2: 多糖 | #3: 糖 | ChemComp-NAG / #4: 糖 | ChemComp-NGA / #5: 化合物 | ChemComp-CA / 研究の焦点であるリガンドがあるか | Y | |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: LRP2 at endosomal pH / タイプ: COMPLEX / 詳細: Endogenously purified from mouse kidney / Entity ID: #1 / 由来: NATURAL |
---|---|
分子量 | 実験値: NO |
由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
緩衝液 | pH: 5.2 |
試料 | 濃度: 2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: OTHER |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 58.06 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EMソフトウェア |
| ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
対称性 | 点対称性: C2 (2回回転対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.97 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 209932 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 57.14 Å2 | ||||||||||||||||||||||||
拘束条件 |
|