登録情報 データベース : EMDB / ID : EMD-45210 ダウンロードとリンクタイトル AP-3 bound to myristoylated Arf1 and LAMPI on a lipid nanodisc; concensus refinement マップデータdeepEMhancer sharpened map 詳細 試料複合体 : AP-3 bound to myristoylated Arf1 and LAMPI on a lipid nanodisc; consensus refinement複合体 : AP-3タンパク質・ペプチド : AP-3 subunit Deltaタンパク質・ペプチド : AP-3 subunit Beta-1タンパク質・ペプチド : AP-3 subunit Mu-1タンパク質・ペプチド : AP-3 subunit Sigma-1複合体 : Arf1タンパク質・ペプチド : ADP-ribosylation factor 1複合体 : LAMPI 詳細 キーワード Adaptor Protein complex / AP-3 / Lysosomal transport / Endosomal transport / Protein trafficking / TRANSPORT 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
synaptic vesicle coating / synaptic vesicle budding from endosome / establishment of protein localization to mitochondrial membrane involved in mitochondrial fission / clathrin-coated vesicle cargo loading, AP-3-mediated / skin epidermis development / AP-type membrane coat adaptor complex / synaptic vesicle membrane organization / regulation of organelle transport along microtubule / zinc ion import into lysosome / AP-3 adaptor complex ... synaptic vesicle coating / synaptic vesicle budding from endosome / establishment of protein localization to mitochondrial membrane involved in mitochondrial fission / clathrin-coated vesicle cargo loading, AP-3-mediated / skin epidermis development / AP-type membrane coat adaptor complex / synaptic vesicle membrane organization / regulation of organelle transport along microtubule / zinc ion import into lysosome / AP-3 adaptor complex / positive regulation of natural killer cell degranulation / neurotransmitter receptor transport, postsynaptic endosome to lysosome / anterograde synaptic vesicle transport / granzyme-mediated programmed cell death signaling pathway / phagolysosome membrane / microvesicle / Golgi to lysosome transport / endosome to melanosome transport / mitotic cleavage furrow ingression / trans-Golgi Network Vesicle Budding / Golgi to vacuole transport / establishment of protein localization to organelle / cytolytic granule membrane / synaptic vesicle recycling / postsynaptic recycling endosome / presynaptic endosome / clathrin adaptor complex / platelet dense granule organization / Glycosphingolipid transport / regulation of receptor internalization / melanosome assembly / granulocyte differentiation / Intra-Golgi traffic / regulation of Arp2/3 complex-mediated actin nucleation / postsynaptic neurotransmitter receptor internalization / GTP-dependent protein binding / positive regulation of NK T cell differentiation / Synthesis of PIPs at the Golgi membrane / clathrin-coated vesicle membrane / lysosomal lumen acidification / positive regulation of natural killer cell mediated cytotoxicity / antigen processing and presentation, exogenous lipid antigen via MHC class Ib / protein targeting to vacuole / protein targeting to lysosome / melanosome organization / respiratory system process / anterograde axonal transport / Nef Mediated CD4 Down-regulation / intracellular zinc ion homeostasis / dendritic spine organization / protein localization to membrane / protein localization to cell surface / long-term synaptic depression / azurophil granule membrane / lysosome organization / COPI-dependent Golgi-to-ER retrograde traffic / Lysosome Vesicle Biogenesis / toll-like receptor signaling pathway / ion channel inhibitor activity / Golgi Associated Vesicle Biogenesis / cell leading edge / lung morphogenesis / Association of TriC/CCT with target proteins during biosynthesis / Synthesis of PIPs at the plasma membrane / autolysosome / autophagosome membrane / ficolin-1-rich granule membrane / homeostasis of number of cells / intracellular copper ion homeostasis / single fertilization / intracellular transport / hematopoietic progenitor cell differentiation / COPI-mediated anterograde transport / transport vesicle / vesicle-mediated transport / axon cytoplasm / multivesicular body / MHC class II antigen presentation / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / cytoplasmic vesicle membrane / sarcomere / small monomeric GTPase / intracellular protein transport / mRNA transcription by RNA polymerase II / terminal bouton / cell morphogenesis / sarcolemma / protein modification process / small GTPase binding / cellular response to virus / endocytosis / blood coagulation / Signaling by BRAF and RAF1 fusions / late endosome membrane / late endosome / synaptic vesicle / insulin receptor signaling pathway / melanosome / presynapse / virus receptor activity 類似検索 - 分子機能 AP-3 complex subunit sigma / AP-3 complex subunit delta domain, metazoa / AP-3 complex subunit delta-1 / Bovine leukaemia virus receptor (BLVR) / AP-3 complex subunit beta, C-terminal domain / AP-3 complex subunit beta 1, serine-rich domain / : / Clathrin-adaptor complex-3 beta-1 subunit C-terminal / Serine-rich region of AP3B1, clathrin-adaptor complex / AP-3 complex subunit beta-1, C-terminal domain ... AP-3 complex subunit sigma / AP-3 complex subunit delta domain, metazoa / AP-3 complex subunit delta-1 / Bovine leukaemia virus receptor (BLVR) / AP-3 complex subunit beta, C-terminal domain / AP-3 complex subunit beta 1, serine-rich domain / : / Clathrin-adaptor complex-3 beta-1 subunit C-terminal / Serine-rich region of AP3B1, clathrin-adaptor complex / AP-3 complex subunit beta-1, C-terminal domain / Clathrin-adaptor complex-3 beta-1 subunit C-terminal / Adaptor protein complex AP-3, delta subunit / Lysosome-associated membrane glycoprotein, conserved site / AP-3 complex subunit beta / : / Lysosome-associated membrane glycoprotein 2, transmembrane segment / Lysosome-associated membrane glycoproteins duplicated domain signature. / LAMP glycoproteins transmembrane and cytoplasmic domain signature. / Lysosome-associated membrane glycoprotein / : / Lysosome-associated membrane glycoprotein 2-like, luminal domains / Lysosome-associated membrane glycoprotein family profile. / Adaptor protein complex, sigma subunit / Beta-adaptin appendage, C-terminal subdomain / Beta2-adaptin appendage, C-terminal sub-domain / ADP-ribosylation factor 1-5 / AP complex subunit beta / Clathrin adaptor complex, small chain / Clathrin adaptor complexes small chain signature. / Clathrin adaptor complexes medium chain signature 1. / Clathrin adaptor, mu subunit / Clathrin adaptor, mu subunit, conserved site / Clathrin adaptor complexes medium chain signature 2. / : / AP complex, mu/sigma subunit / Clathrin adaptor complex small chain / Adaptor complexes medium subunit family / AP-2 complex subunit mu, C-terminal superfamily / Clathrin/coatomer adaptor, adaptin-like, N-terminal / Adaptin N terminal region / Mu homology domain / Mu homology domain (MHD) profile. / Small GTPase superfamily, ARF type / small GTPase Arf family profile. / Sar1p-like members of the Ras-family of small GTPases / Small GTPase superfamily, ARF/SAR type / ADP-ribosylation factor family / Longin-like domain superfamily / ARF-like small GTPases; ARF, ADP-ribosylation factor / Rab subfamily of small GTPases / Armadillo-like helical / Small GTP-binding protein domain / Armadillo-type fold / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 AP-3 complex subunit beta-1 / AP-3 complex subunit delta-1 / Lysosome-associated membrane glycoprotein 1 / ADP-ribosylation factor 1 / AP-3 complex subunit sigma-1 / AP-3 complex subunit mu-1 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 : 4.2 Å 詳細 データ登録者Baker RW / Begley M 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) R35 GM150960 米国
引用ジャーナル : Proc Natl Acad Sci U S A / 年 : 2024タイトル : A structure-based mechanism for initiation of AP-3 coated vesicle formation.著者 : Matthew Begley / Mahira Aragon / Richard W Baker / 要旨 : Adaptor protein complex-3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 adopts a constitutively open conformation ... Adaptor protein complex-3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 adopts a constitutively open conformation compared to the related AP-1 and AP-2 coat complexes, which are inactive until undergoing large conformational changes upon membrane recruitment. How AP-3 is regulated is therefore an open question. To understand the mechanism of AP-3 membrane recruitment and activation, we reconstituted human AP-3 and determined multiple structures in the soluble and membrane-bound states using electron cryo-microscopy. Similar to yeast AP-3, human AP-3 is in a constitutively open conformation. To reconstitute AP-3 activation by adenosine di-phosphate (ADP)-ribosylation factor 1 (Arf1), a small guanosine tri-phosphate (GTP)ase, we used lipid nanodiscs to build Arf1-AP-3 complexes on membranes and determined three structures showing the stepwise conformational changes required for formation of AP-3 coated vesicles. First, membrane recruitment is driven by one of two predicted Arf1 binding sites, which flexibly tethers AP-3 to the membrane. Second, cargo binding causes AP-3 to adopt a fixed position and rigidifies the complex, which stabilizes binding for a second Arf1 molecule. Finally, binding of the second Arf1 molecule provides the template for AP-3 dimerization, providing a glimpse into the first step of coat polymerization. We propose coat polymerization only occurs after cargo engagement, thereby linking cargo sorting with assembly of higher-order coat structures. Additionally, we provide evidence for two amphipathic helices in AP-3, suggesting that AP-3 contributes to membrane deformation during coat assembly. In total, these data provide evidence for the first stages of AP-3-mediated vesicle coat assembly. 履歴 登録 2024年6月6日 - ヘッダ(付随情報) 公開 2024年12月18日 - マップ公開 2024年12月18日 - 更新 2025年3月5日 - 現状 2025年3月5日 処理サイト : RCSB / 状態 : 公開
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