- EMDB-45787: Nanobody 4 bound to Apolipoprotein B 100 -
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基本情報
登録情報
データベース: EMDB / ID: EMD-45787
タイトル
Nanobody 4 bound to Apolipoprotein B 100
マップデータ
Map File
試料
複合体: Middle of ApoB100 bound to LDL receptor and Legobody
タンパク質・ペプチド: Apolipoprotein B 100
タンパク質・ペプチド: Maltodextrin-binding protein,Immunoglobulin G-binding protein A,Immunoglobulin G-binding protein G
タンパク質・ペプチド: Legobody 8D3 Fab Heavy Chain
タンパク質・ペプチド: Legobody 8D3 Fab Light Chain
タンパク質・ペプチド: ApoB100 nanobody 4
タンパク質・ペプチド: Low-density lipoprotein receptor
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
リガンド: CALCIUM ION
キーワード
Apolipoprotein B 100 / ApoB100 / LDLreceptor / LIPID TRANSPORT
機能・相同性
機能・相同性情報
mature chylomicron / Scavenging by Class H Receptors / triglyceride mobilization / positive regulation of cholesterol storage / regulation of cholesterol biosynthetic process / VLDL assembly / receptor-mediated endocytosis involved in cholesterol transport / regulation of phosphatidylcholine catabolic process / lipase binding / plasma lipoprotein particle clearance ...mature chylomicron / Scavenging by Class H Receptors / triglyceride mobilization / positive regulation of cholesterol storage / regulation of cholesterol biosynthetic process / VLDL assembly / receptor-mediated endocytosis involved in cholesterol transport / regulation of phosphatidylcholine catabolic process / lipase binding / plasma lipoprotein particle clearance / LDL remodeling / Scavenging by Class B Receptors / positive regulation of lysosomal protein catabolic process / negative regulation of astrocyte activation / VLDL clearance / triglyceride catabolic process / negative regulation of microglial cell activation / very-low-density lipoprotein particle receptor activity / very-low-density lipoprotein particle assembly / PCSK9-LDLR complex / cholesterol import / low-density lipoprotein particle clearance / clathrin heavy chain binding / negative regulation of receptor recycling / positive regulation of triglyceride biosynthetic process / intestinal cholesterol absorption / negative regulation of low-density lipoprotein particle clearance / chylomicron remnant / low-density lipoprotein particle receptor activity / intermediate-density lipoprotein particle / response to caloric restriction / Chylomicron clearance / low-density lipoprotein particle binding / amyloid-beta clearance by cellular catabolic process / positive regulation of macrophage derived foam cell differentiation / positive regulation of lipid storage / Chylomicron remodeling / cellular response to lipoprotein particle stimulus / regulation of protein metabolic process / flagellated sperm motility / Chylomicron assembly / Regulation of TLR by endogenous ligand / LDL clearance / high-density lipoprotein particle clearance / chylomicron / lipoprotein catabolic process / phospholipid transport / low-density lipoprotein particle / lipoprotein biosynthetic process / cholesterol transfer activity / cholesterol transport / very-low-density lipoprotein particle / low-density lipoprotein particle remodeling / endolysosome membrane / negative regulation of amyloid fibril formation / fertilization / IgG binding / cholesterol efflux / artery morphogenesis / Scavenging by Class A Receptors / lipoprotein transport / cellular response to fatty acid / negative regulation of protein metabolic process / regulation of cholesterol metabolic process / low-density lipoprotein particle receptor binding / Platelet sensitization by LDL / Scavenging by Class F Receptors / sorting endosome / amyloid-beta clearance / lipoprotein particle binding / endoplasmic reticulum exit site / cellular response to low-density lipoprotein particle stimulus / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / long-term memory / smooth endoplasmic reticulum / phagocytosis / Retinoid metabolism and transport / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / clathrin-coated pit / somatodendritic compartment / lipid droplet / endocytic vesicle lumen / receptor-mediated endocytosis / cholesterol metabolic process / lysosomal lumen / post-embryonic development / cholesterol homeostasis / endosome lumen / establishment of localization in cell / Cell surface interactions at the vascular wall / Post-translational protein phosphorylation / clathrin-coated endocytic vesicle membrane / Heme signaling / response to virus / lipid metabolic process / phospholipid binding / positive regulation of inflammatory response 類似検索 - 分子機能
Lipid transport, open beta-sheet / Apolipoprotein B100 C-terminal / : / Domain of Unknown Function (DUF1081) / Apolipoprotein B100 C terminal / Vitellinogen, open beta-sheet, subdomain 1 / Vitellinogen, open beta-sheet / Vitellinogen, open beta-sheet / DUF1943 / Vitellogenin, N-terminal ...Lipid transport, open beta-sheet / Apolipoprotein B100 C-terminal / : / Domain of Unknown Function (DUF1081) / Apolipoprotein B100 C terminal / Vitellinogen, open beta-sheet, subdomain 1 / Vitellinogen, open beta-sheet / Vitellinogen, open beta-sheet / DUF1943 / Vitellogenin, N-terminal / Lipovitellin-phosvitin complex, superhelical domain / Vitellinogen, beta-sheet N-terminal / Lipid transport protein, beta-sheet shell / Lipoprotein amino terminal region / Vitellogenin domain profile. / Lipoprotein N-terminal Domain / Octapeptide repeat / Octapeptide repeat / : / Protein A, Ig-binding domain / B domain / IgG-binding B / B domain / M protein-type anchor domain / GA-like domain / GA-like domain / Low-density lipoprotein receptor repeat class B / LDL-receptor class B (LDLRB) repeat profile. / Lysin motif / LDLR class B repeat / Low-density lipoprotein-receptor YWTD domain / LysM domain superfamily / LysM domain profile. / LysM domain / LysM domain / Immunoglobulin/albumin-binding domain superfamily / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A, conserved site / LDL-receptor class A (LDLRA) domain signature. / YSIRK type signal peptide / LDL-receptor class A (LDLRA) domain profile. / : / Calcium-binding EGF domain / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A repeat / LDL receptor-like superfamily / YSIRK Gram-positive signal peptide / Six-bladed beta-propeller, TolB-like / LPXTG cell wall anchor motif / Coagulation Factor Xa inhibitory site / Gram-positive cocci surface proteins LPxTG motif profile. / LPXTG cell wall anchor domain / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / EGF-type aspartate/asparagine hydroxylation site / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / 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 / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein / Epidermal growth factor-like domain. / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 2. / EGF-like domain / Armadillo-type fold 類似検索 - ドメイン・相同性
Maltodextrin-binding protein / Low-density lipoprotein receptor / Apolipoprotein B-100 / Immunoglobulin G-binding protein G / Immunoglobulin G-binding protein A 類似検索 - 構成要素
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
米国
引用
ジャーナル: Nature / 年: 2025 タイトル: Structure of apolipoprotein B100 bound to the low-density lipoprotein receptor. 著者: Mart Reimund / Altaira D Dearborn / Giorgio Graziano / Haotian Lei / Anthony M Ciancone / Ashish Kumar / Ronald Holewinski / Edward B Neufeld / Francis J O'Reilly / Alan T Remaley / Joseph Marcotrigiano / 要旨: Apolipoprotein B100 (apoB100) is a structural component of low-density lipoprotein (LDL) and a ligand for the LDL receptor (LDLR). Mutations in apoB100 or in LDLR cause familial ...Apolipoprotein B100 (apoB100) is a structural component of low-density lipoprotein (LDL) and a ligand for the LDL receptor (LDLR). Mutations in apoB100 or in LDLR cause familial hypercholesterolaemia, an autosomal dominant disease that is characterized by a marked increase in LDL cholesterol (LDL-C) and a higher risk of cardiovascular disease. The structure of apoB100 on LDL and its interaction with LDLR are poorly understood. Here we present the cryo-electron microscopy structures of apoB100 on LDL bound to the LDLR and a nanobody complex, which can form a C-symmetric, higher-order complex. Using local refinement, we determined high-resolution structures of the interfaces between apoB100 and LDLR. One binding interface is formed between several small-ligand-binding modules of LDLR and a series of basic patches that are scattered along a β-belt formed by apoB100, encircling LDL. The other binding interface is formed between the β-propeller domain of LDLR and the N-terminal domain of apoB100. Our results reveal how both interfaces are involved in LDL dimer formation, and how LDLR cycles between LDL- and self-bound conformations. In addition, known mutations in either apoB100 or LDLR, associated with high levels of LDL-C, are located at the LDL-LDLR interface.