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基本情報
登録情報 | データベース: EMDB / ID: EMD-20217 | |||||||||
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タイトル | Structure of SIVsmm Nef and SMM tetherin bound to the clathrin adaptor AP-2 complex | |||||||||
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![]() | AP / HIV / Nef / trafficking / Protein transport / viral restriction factor | |||||||||
機能・相同性 | ![]() AP-type membrane coat adaptor complex / Formation of annular gap junctions / Gap junction degradation / LDL clearance / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / WNT5A-dependent internalization of FZD4 / clathrin coat / postsynaptic endocytic zone / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / LDL clearance ...AP-type membrane coat adaptor complex / Formation of annular gap junctions / Gap junction degradation / LDL clearance / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / WNT5A-dependent internalization of FZD4 / clathrin coat / postsynaptic endocytic zone / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / LDL clearance / Retrograde neurotrophin signalling / Trafficking of GluR2-containing AMPA receptors / VLDLR internalisation and degradation / Retrograde neurotrophin signalling / WNT5A-dependent internalization of FZD4 / VLDLR internalisation and degradation / extrinsic component of presynaptic endocytic zone membrane / clathrin adaptor complex / cardiac septum development / metalloendopeptidase inhibitor activity / Recycling pathway of L1 / MHC class II antigen presentation / AP-2 adaptor complex / regulation of vesicle size / postsynaptic neurotransmitter receptor internalization / clathrin coat assembly / Cargo recognition for clathrin-mediated endocytosis / Recycling pathway of L1 / Clathrin-mediated endocytosis / positive regulation of synaptic vesicle endocytosis / Cargo recognition for clathrin-mediated endocytosis / clathrin adaptor activity / Clathrin-mediated endocytosis / membrane coat / vesicle budding from membrane / positive regulation of protein localization to membrane / clathrin-dependent endocytosis / MHC class II antigen presentation / signal sequence binding / coronary vasculature development / aorta development / ventricular septum development / Neutrophil degranulation / clathrin binding / low-density lipoprotein particle receptor binding / Trafficking of GluR2-containing AMPA receptors / positive regulation of endocytosis / positive regulation of receptor internalization / synaptic vesicle endocytosis / negative regulation of protein localization to plasma membrane / vesicle-mediated transport / protein serine/threonine kinase binding / phosphatidylinositol binding / secretory granule / kidney development / intracellular protein transport / cytoplasmic side of plasma membrane / kinase binding / disordered domain specific binding / synaptic vesicle / heart development / protein-containing complex assembly / cytoplasmic vesicle / defense response to virus / transmembrane transporter binding / postsynapse / protein domain specific binding / innate immune response / intracellular membrane-bounded organelle / synapse / lipid binding / protein-containing complex binding / protein kinase binding / GTP binding / host cell plasma membrane / glutamatergic synapse / cell surface / Golgi apparatus / mitochondrion / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() ![]() ![]() | |||||||||
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 | |||||||||
![]() | Buffalo CZ / Ren X | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral Transmission. 著者: Cosmo Z Buffalo / Christina M Stürzel / Elena Heusinger / Dorota Kmiec / Frank Kirchhoff / James H Hurley / Xuefeng Ren / ![]() ![]() 要旨: Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 ...Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif. As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmission of non-human primate lentiviruses. To determine the molecular basis for tetherin counteraction, we reconstituted the AP-2 complex with a simian tetherin and SIV Nef and determined its structure by cryoelectron microscopy (cryo-EM). Nef refolds the first α-helix of the β2 subunit of AP-2 to a β hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of most other Nef substrates, including MHC class I, CD3, and CD4 but overlaps with the site for the restriction factor SERINC5. This structure explains the dependence of SIVs on tetherin DIWK and consequent barrier to human transmission. | |||||||||
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 1.2 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 21.2 KB 21.2 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.3 KB | 表示 | ![]() |
画像 | ![]() | 205.6 KB | ||
Filedesc metadata | ![]() | 7.8 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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「今月の分子」の関連する項目 |
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.149 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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試料の構成要素
-全体 : Structure of SIVsmm Nef and SMM tetherin bound to the clathrin ad...
全体 | 名称: Structure of SIVsmm Nef and SMM tetherin bound to the clathrin adaptor AP-2 complex |
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要素 |
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-超分子 #1: Structure of SIVsmm Nef and SMM tetherin bound to the clathrin ad...
超分子 | 名称: Structure of SIVsmm Nef and SMM tetherin bound to the clathrin adaptor AP-2 complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 203.6 KDa |
-分子 #1: AP-2 complex subunit alpha
分子 | 名称: AP-2 complex subunit alpha / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 104.286391 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MPAVSKGEGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC KLLFIFLLGH DIDFGHMEAV NLLSSNRYT EKQIGYLFIS VLVNSNSELI RLINNAIKND LASRNPTFMG LALHCIANVG SREMAEAFAG EIPKILVAGD T MDSVKQSA ...文字列: MPAVSKGEGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC KLLFIFLLGH DIDFGHMEAV NLLSSNRYT EKQIGYLFIS VLVNSNSELI RLINNAIKND LASRNPTFMG LALHCIANVG SREMAEAFAG EIPKILVAGD T MDSVKQSA ALCLLRLYRT SPDLVPMGDW TSRVVHLLND QHLGVVTAAT SLITTLAQKN PEEFKTSVSL AVSRLSRIVT SA STDLQDY TYYFVPAPWL SVKLLRLLQC YPPPEDPAVR GRLTECLETI LNKAQEPPKS KKVQHSNAKN AVLFEAISLI IHH DSEPNL LVRACNQLGQ FLQHRETNLR YLALESMCTL ASSEFSHEAV KTHIETVINA LKTERDVSVR QRAVDLLYAM CDRS NAQQI VAEMLSYLET ADYSIREEIV LKVAILAEKY AVDYTWYVDT ILNLIRIAGD YVSEEVWYRV IQIVINRDDV QGYAA KTVF EALQAPACHE NLVKVGGYIL GEFGNLIAGD PRSSPLIQFN LLHSKFHLCS VPTRALLLST YIKFVNLFPE VKATIQ DVL RSDSQLKNAD VELQQRAVEY LRLSTVASTD ILATVLEEMP PFPERESSIL AKLKKKKGPS TVTDLEETKR ERSIDVN GG PEPVPASTSA ASTPSPSADL LGLGAVPPAP TGPPPTSGGG LLVDVFSDSA SAVAPLAPGS EDNFARFVCK NNGVLFEN Q LLQIGLKSEF RQNLGRMFIF YGNKTSTQFL NFTPTLICAD DLQTNLNLQT KPVDPTVDGG AQVQQVVNIE CISDFTEAP VLNIQFRYGG TFQNVSVKLP ITLNKFFQPT EMASQDFFQR WKQLSNPQQE VQNIFKAKHP MDTEITKAKI IGFGSALLEE VDPNPANFV GAGIIHTKTT QIGCLLRLEP NLQAQMYRLT LRTSKDTVSQ RLCELLSEQF UniProtKB: AP-2 complex subunit alpha |
-分子 #2: AP-2 complex subunit beta
分子 | 名称: AP-2 complex subunit beta / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 66.953195 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MTDSKYFTTN KKGEIFELKA ELNNEKKEKR KEAVKKVIAA MTVGKDVSSL FPDVVNCMQT DNLELKKLVY LYLMNYAKSQ PDMAIMAVN SFVKDCEDPN PLIRALAVRT MGCIRVDKIT EYLCEPLRKC LKDEDPYVRK TAAVCVAKLH DINAQMVEDQ G FLDSLRDL ...文字列: MTDSKYFTTN KKGEIFELKA ELNNEKKEKR KEAVKKVIAA MTVGKDVSSL FPDVVNCMQT DNLELKKLVY LYLMNYAKSQ PDMAIMAVN SFVKDCEDPN PLIRALAVRT MGCIRVDKIT EYLCEPLRKC LKDEDPYVRK TAAVCVAKLH DINAQMVEDQ G FLDSLRDL IADSNPMVVA NAVAALSEIS ESHPNSNLLD LNPQNINKLL TALNECTEWG QIFILDCLSN YNPKDDREAQ SI CERVTPR LSHANSAVVL SAVKVLMKFL ELLPKDSDYY NMLLKKLAPP LVTLLSGEPE VQYVALRNIN LIVQKRPEIL KQE IKVFFV KYNDPIYVKL EKLDIMIRLA SQANIAQVLA ELKEYATEVD VDFVRKAVRA IGRCAIKVEQ SAERCVSTLL DLIQ TKVNY VVQEAIVVIR DIFRKYPNKY ESIIATLCEN LDSLDEPDAR AAMIWIVGEY AERIDNADEL LESFLEGFHD ESTQV QLTL LTAIVKLFLK KPSETQELVQ QVLSLATQDS DNPDLRDRGY IYWRLLSTDP VTAKEVVLSE KPLISEETDL IEPTLL DEL ICHIGSLASV YHKPPNAFVE GSHGIHRK UniProtKB: AP-2 complex subunit beta |
-分子 #3: Adaptor protein complex AP-2, mu1
分子 | 名称: Adaptor protein complex AP-2, mu1 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 16.161563 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MIGGLFIYNH KGEVLISRVY RDDIGRNAVD AFRVNVIHAR QQVRSPVTNI ARTSFFHVKR SNIWLAAVTK QNVNAAMVFE FLYKMCDVM AAYFGKISEE NIKNNFVLIY ELLDEILDFG YPQNSETGAL KTFITQQGIK SQ UniProtKB: AP-2 complex subunit mu |
-分子 #4: Tetherin,Protein Nef
分子 | 名称: Tetherin,Protein Nef / タイプ: protein_or_peptide / ID: 4 詳細: protein chimera of the cytoplasmic tail of sooty mangabey (smm) linked to the N-terminus of SIV smm tetherin コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 31.772352 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: ILYDYSRMPM GDIWKEDGDK RSKGSDEASE GSGMGGVTSK KQSKRRQGLR ERLLQARGET DGYSRSRGEL GKGWNLPSAE GQGYSEEQF MNTPWRNPAR EGEKLKYRQQ NMDDVDDDDD ELVGVAVHPK VPLRAMSYKL AIDMSHFIKE KGGLEGIYYS D RRHRILDI ...文字列: ILYDYSRMPM GDIWKEDGDK RSKGSDEASE GSGMGGVTSK KQSKRRQGLR ERLLQARGET DGYSRSRGEL GKGWNLPSAE GQGYSEEQF MNTPWRNPAR EGEKLKYRQQ NMDDVDDDDD ELVGVAVHPK VPLRAMSYKL AIDMSHFIKE KGGLEGIYYS D RRHRILDI YLEKEEGIIP DWQNYTSGPG VRYPLFFGWL WKLVPVNVSD EAQEDETHCL VHPAQTSQWD DPWGEVLAWK FD PKLAYTY EAFIRYPEEF GNDSGLSKEE VKRRLTAR UniProtKB: Tetherin variant Sm2, Protein Nef |
-分子 #5: AP-2 complex subunit sigma
分子 | 名称: AP-2 complex subunit sigma / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 17.011662 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MIRFILIQNR AGKTRLAKWY MQFDDDEKQK LIEEVHAVVT VRDAKHTNFV EFRNFKIIYR RYAGLYFCIC VDVNDNNLAY LEAIHNFVE VLNEYFHCVS ELDLVFNFYK VYTVVDEMFL AGEIRETSQT KVLKQLLMLQ SLE UniProtKB: AP-2 complex subunit sigma |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.7 mg/mL |
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緩衝液 | pH: 8 |
グリッド | モデル: C-flat-2/1 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 30 sec. / 前処理 - 雰囲気: AIR / 前処理 - 気圧: 0.04 kPa / 詳細: 25mA |
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 50.16 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |