登録情報 データベース : EMDB / ID : EMD-40241 ダウンロードとリンクタイトル 1:1:1 agrin/LRP4/MuSK complex マップデータCryo-EM map of 1:1:1 agrin/LRP4/MuSK complex 詳細 試料複合体 : 1:1:1 agrin/LRP4/MuSK complexタンパク質・ペプチド : Agrinタンパク質・ペプチド : Low-density lipoprotein receptor-related protein 4タンパク質・ペプチド : Muscle, skeletal receptor tyrosine-protein kinase 詳細 キーワード agrin / LRP4 / MuSK / NMJ / RTK / SIGNALING PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
positive regulation of presynaptic membrane organization / positive regulation of protein geranylgeranylation / Defective B3GALT6 causes EDSP2 and SEMDJL1 / Defective B4GALT7 causes EDS, progeroid type / Defective B3GAT3 causes JDSSDHD / regulation of synaptic assembly at neuromuscular junction / Defective EXT2 causes exostoses 2 / Defective EXT1 causes exostoses 1, TRPS2 and CHDS / : / clustering of voltage-gated sodium channels ... positive regulation of presynaptic membrane organization / positive regulation of protein geranylgeranylation / Defective B3GALT6 causes EDSP2 and SEMDJL1 / Defective B4GALT7 causes EDS, progeroid type / Defective B3GAT3 causes JDSSDHD / regulation of synaptic assembly at neuromuscular junction / Defective EXT2 causes exostoses 2 / Defective EXT1 causes exostoses 1, TRPS2 and CHDS / : / clustering of voltage-gated sodium channels / positive regulation of synaptic assembly at neuromuscular junction / A tetrasaccharide linker sequence is required for GAG synthesis / skeletal muscle acetylcholine-gated channel clustering / chondroitin sulfate binding / postsynaptic membrane assembly / HS-GAG biosynthesis / presynaptic membrane assembly / HS-GAG degradation / sialic acid binding / negative regulation of axonogenesis / positive regulation of skeletal muscle acetylcholine-gated channel clustering / proximal/distal pattern formation / dystroglycan binding / amyloid-beta clearance by cellular catabolic process / Wnt-protein binding / NCAM1 interactions / dorsal/ventral pattern formation / synaptic assembly at neuromuscular junction / positive regulation of kinase activity / negative regulation of ossification / heparan sulfate proteoglycan binding / dendrite morphogenesis / limb development / positive regulation of filopodium assembly / neuromuscular junction development / embryonic digit morphogenesis / generation of neurons / receptor clustering / odontogenesis of dentin-containing tooth / plasma membrane raft / apolipoprotein binding / Non-integrin membrane-ECM interactions / basement membrane / hair follicle development / ECM proteoglycans / Integrin cell surface interactions / Retinoid metabolism and transport / laminin binding / cell surface receptor protein tyrosine kinase signaling pathway / transmembrane receptor protein tyrosine kinase activity / lysosomal lumen / positive regulation of GTPase activity / synaptic membrane / kidney development / synapse organization / negative regulation of canonical Wnt signaling pathway / neuromuscular junction / G protein-coupled acetylcholine receptor signaling pathway / receptor protein-tyrosine kinase / structural constituent of cytoskeleton / receptor tyrosine kinase binding / memory / Wnt signaling pathway / positive regulation of neuron projection development / Golgi lumen / endocytosis / positive regulation of peptidyl-tyrosine phosphorylation / scaffold protein binding / postsynaptic membrane / protein tyrosine kinase activity / collagen-containing extracellular matrix / protein autophosphorylation / Attachment and Entry / postsynaptic density / cell differentiation / receptor complex / positive regulation of protein phosphorylation / neuronal cell body / synapse / calcium ion binding / dendrite / positive regulation of gene expression / cell surface / signal transduction / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular exosome / extracellular region / ATP binding / metal ion binding / plasma membrane 類似検索 - 分子機能 NtA (N-terminal agrin) domain / Agrin NtA domain / NtA (N-terminal agrin) domain profile. / Follistatin-like, N-terminal / Follistatin-N-terminal domain-like / Factor I / membrane attack complex / factor I membrane attack complex / Domain found in sea urchin sperm protein, enterokinase, agrin / Laminin G domain / Laminin-type EGF-like (LE) domain profile. ... NtA (N-terminal agrin) domain / Agrin NtA domain / NtA (N-terminal agrin) domain profile. / Follistatin-like, N-terminal / Follistatin-N-terminal domain-like / Factor I / membrane attack complex / factor I membrane attack complex / Domain found in sea urchin sperm protein, enterokinase, agrin / Laminin G domain / Laminin-type EGF-like (LE) domain profile. / Laminin-type EGF-like (LE) domain signature. / Laminin-type epidermal growth factor-like domai / Laminin EGF domain / SEA domain superfamily / Kazal-type serine protease inhibitor domain / Complement Clr-like EGF domain / Laminin-type EGF domain / Complement Clr-like EGF-like / Kazal-type serine protease inhibitor domain / SEA domain profile. / SEA domain / SEA domain / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / Laminin G domain profile. / Kazal type serine protease inhibitors / Laminin G domain / Low-density lipoprotein receptor repeat class B / LDL-receptor class B (LDLRB) repeat profile. / Laminin G domain / LDLR class B repeat / Low-density lipoprotein-receptor YWTD domain / Kazal domain superfamily / Kazal domain / Kazal domain profile. / Tissue inhibitor of metalloproteinases-like, OB-fold / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A, conserved site / LDL-receptor class A (LDLRA) domain signature. / 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-like domain / Immunoglobulin domain / 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 / Immunoglobulin I-set / Immunoglobulin I-set domain / Epidermal growth factor-like domain. / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 2. / EGF-like domain signature 1. / EGF-like domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Concanavalin A-like lectin/glucanase domain superfamily / Immunoglobulin subtype / Immunoglobulin / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Agrin / Muscle, skeletal receptor tyrosine-protein kinase / Low-density lipoprotein receptor-related protein 4 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.8 Å 詳細 データ登録者Xie T / Xu GJ / Liu Y / Quade B / Lin WC / Bai XC 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R01GM143158 米国
引用ジャーナル : Proc Natl Acad Sci U S A / 年 : 2023タイトル : Structural insights into the assembly of the agrin/LRP4/MuSK signaling complex.著者 : Tian Xie / Guangjun Xu / Yun Liu / Bradley Quade / Weichun Lin / Xiao-Chen Bai / 要旨 : MuSK is a receptor tyrosine kinase (RTK) that plays essential roles in the formation and maintenance of the neuromuscular junction. Distinct from most members of RTK family, MuSK activation requires ... MuSK is a receptor tyrosine kinase (RTK) that plays essential roles in the formation and maintenance of the neuromuscular junction. Distinct from most members of RTK family, MuSK activation requires not only its cognate ligand agrin but also its coreceptors LRP4. However, how agrin and LRP4 coactivate MuSK remains unclear. Here, we report the cryo-EM structure of the extracellular ternary complex of agrin/LRP4/MuSK in a stoichiometry of 1:1:1. This structure reveals that arc-shaped LRP4 simultaneously recruits both agrin and MuSK to its central cavity, thereby promoting a direct interaction between agrin and MuSK. Our cryo-EM analyses therefore uncover the assembly mechanism of agrin/LRP4/MuSK signaling complex and reveal how MuSK receptor is activated by concurrent binding of agrin and LRP4. 履歴 登録 2023年3月29日 - ヘッダ(付随情報) 公開 2023年5月17日 - マップ公開 2023年5月17日 - 更新 2023年6月14日 - 現状 2023年6月14日 処理サイト : RCSB / 状態 : 公開
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