+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-40989 | ||||||||||||
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タイトル | Cryo-EM Structures of Full-length Integrin alphaIIbbeta3 in Native Lipids | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | complex / open headpiece / CELL ADHESION (細胞接着) | ||||||||||||
機能・相同性 | 機能・相同性情報 tube development / regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / alpha9-beta1 integrin-ADAM8 complex / regulation of trophoblast cell migration / regulation of postsynaptic neurotransmitter receptor diffusion trapping / alphav-beta3 integrin-vitronectin complex / regulation of extracellular matrix organization / platelet alpha granule membrane / positive regulation of glomerular mesangial cell proliferation ...tube development / regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / alpha9-beta1 integrin-ADAM8 complex / regulation of trophoblast cell migration / regulation of postsynaptic neurotransmitter receptor diffusion trapping / alphav-beta3 integrin-vitronectin complex / regulation of extracellular matrix organization / platelet alpha granule membrane / positive regulation of glomerular mesangial cell proliferation / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / alphav-beta3 integrin-PKCalpha complex / maintenance of postsynaptic specialization structure / fibrinogen binding / alphav-beta3 integrin-HMGB1 complex / blood coagulation, fibrin clot formation / negative regulation of lipid transport / vascular endothelial growth factor receptor 2 binding / glycinergic synapse / negative regulation of low-density lipoprotein receptor activity / regulation of release of sequestered calcium ion into cytosol / angiogenesis involved in wound healing / Elastic fibre formation / cell-substrate junction assembly / mesodermal cell differentiation / alphav-beta3 integrin-IGF-1-IGF1R complex / platelet-derived growth factor receptor binding / filopodium membrane / extracellular matrix binding / positive regulation of fibroblast migration / regulation of postsynaptic neurotransmitter receptor internalization / positive regulation of vascular endothelial growth factor receptor signaling pathway / apolipoprotein A-I-mediated signaling pathway / regulation of bone resorption / apoptotic cell clearance / wound healing, spreading of epidermal cells / positive regulation of cell adhesion mediated by integrin / heterotypic cell-cell adhesion / integrin complex / Molecules associated with elastic fibres / positive regulation of leukocyte migration / positive regulation of cell-matrix adhesion / cellular response to insulin-like growth factor stimulus / smooth muscle cell migration / microvillus membrane / cell adhesion mediated by integrin / Syndecan interactions / negative chemotaxis / p130Cas linkage to MAPK signaling for integrins / activation of protein kinase activity / cellular response to platelet-derived growth factor stimulus / cell-substrate adhesion / protein disulfide isomerase activity / positive regulation of smooth muscle cell migration / positive regulation of osteoblast proliferation / TGF-beta receptor signaling activates SMADs / PECAM1 interactions / lamellipodium membrane / GRB2:SOS provides linkage to MAPK signaling for Integrins / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / platelet-derived growth factor receptor signaling pathway / fibronectin binding / ECM proteoglycans / positive regulation of T cell migration / positive regulation of bone resorption / Integrin cell surface interactions / coreceptor activity / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / cell adhesion molecule binding / positive regulation of endothelial cell proliferation / 着床 / positive regulation of endothelial cell migration / Integrin signaling / substrate adhesion-dependent cell spreading / cell-matrix adhesion / Signal transduction by L1 / response to activity / integrin-mediated signaling pathway / regulation of actin cytoskeleton organization / protein kinase C binding / positive regulation of smooth muscle cell proliferation / Signaling by high-kinase activity BRAF mutants / wound healing / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / MAP2K and MAPK activation / 凝固・線溶系 / 血小板 / ruffle membrane / VEGFA-VEGFR2 Pathway / 細胞接着 / cellular response to mechanical stimulus / positive regulation of angiogenesis / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / regulation of protein localization 類似検索 - 分子機能 | ||||||||||||
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: 3.4 Å | ||||||||||||
データ登録者 | Adair B / Xiong JP / Yeager M / Arnaout MA | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Cryo-EM structures of full-length integrin αIIbβ3 in native lipids. 著者: Brian D Adair / Jian-Ping Xiong / Mark Yeager / M Amin Arnaout / 要旨: Platelet integrin αIIbβ3 is maintained in a bent inactive state (low affinity to physiologic ligand), but can rapidly switch to a ligand-competent (high-affinity) state in response to intracellular ...Platelet integrin αIIbβ3 is maintained in a bent inactive state (low affinity to physiologic ligand), but can rapidly switch to a ligand-competent (high-affinity) state in response to intracellular signals ("inside-out" activation). Once bound, ligands drive proadhesive "outside-in" signaling. Anti-αIIbβ3 drugs like eptifibatide can engage the inactive integrin directly, inhibiting thrombosis but inadvertently impairing αIIbβ3 hemostatic functions. Bidirectional αIIbβ3 signaling is mediated by reorganization of the associated αIIb and β3 transmembrane α-helices, but the underlying changes remain poorly defined absent the structure of the full-length receptor. We now report the cryo-EM structures of full-length αIIbβ3 in its apo and eptifibatide-bound states in native cell-membrane nanoparticles at near-atomic resolution. The apo form adopts the bent inactive state but with separated transmembrane α-helices, and a fully accessible ligand-binding site that challenges the model that this site is occluded by the plasma membrane. Bound eptifibatide triggers dramatic conformational changes that may account for impaired hemostasis. These results advance our understanding of integrin structure and function and may guide development of safer inhibitors. | ||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_40989.map.gz | 51.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-40989-v30.xml emd-40989.xml | 19.9 KB 19.9 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_40989_fsc.xml | 9.9 KB | 表示 | FSCデータファイル |
画像 | emd_40989.png | 85.6 KB | ||
Filedesc metadata | emd-40989.cif.gz | 7.3 KB | ||
その他 | emd_40989_half_map_1.map.gz emd_40989_half_map_2.map.gz | 95.7 MB 95.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-40989 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40989 | HTTPS FTP |
-関連構造データ
関連構造データ | 8t2vMC 8t2uC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_40989.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.08 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
ファイル | emd_40989_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_40989_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : full length integrin alphaIIbbeta3
全体 | 名称: full length integrin alphaIIbbeta3 |
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要素 |
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-超分子 #1: full length integrin alphaIIbbeta3
超分子 | 名称: full length integrin alphaIIbbeta3 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Integrin alpha-IIb
分子 | 名称: Integrin alpha-IIb / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 110.106391 KDa |
配列 | 文字列: LNLDPVQLTF YAGPNGSQFG FSLDFHKDSH GRVAIVVGAP RTLGPSQEET GGVFLCPWRA EGGQCPSLLF DLRDETRNVG SQTLQTFKA RQGLGASVVS WSDVIVACAP WQHWNVLEKT EEAEKTPVGS CFLAQPESGR RAEYSPCRGN TLSRIYVEND F SWDKRYCE ...文字列: LNLDPVQLTF YAGPNGSQFG FSLDFHKDSH GRVAIVVGAP RTLGPSQEET GGVFLCPWRA EGGQCPSLLF DLRDETRNVG SQTLQTFKA RQGLGASVVS WSDVIVACAP WQHWNVLEKT EEAEKTPVGS CFLAQPESGR RAEYSPCRGN TLSRIYVEND F SWDKRYCE AGFSSVVTQA GELVLGAPGG YYFLGLLAQA PVADIFSSYR PGILLWHVSS QSLSFDSSNP EYFDGYWGYS VA VGEFDGD LNTTEYVVGA PTWSWTLGAV EILDSYYQRL HRLRGEQMAS YFGHSVAVTD VNGDGRHDLL VGAPLYMESR ADR KLAEVG RVYLFLQPRG PHALGAPSLL LTGTQLYGRF GSAIAPLGDL DRDGYNDIAV AAPYGGPSGR GQVLVFLGQS EGLR SRPSQ VLDSPFPTGS AFGFSLRGAV DIDDNGYPDL IVGAYGANQV AVYRAQPVVK ASVQLLVQDS LNPAVKSCVL PQTKT PVSC FNIQMCVGAT GHNIPQKLSL NAELQLDRQK PRQGRRVLLL GSQQAGTTLN LDLGGKHSPI CHTTMAFLRD EADFRD KLS PIVLSLNVSL PPTEAGMAPA VVLHGDTHVQ EQTRIVLDCG EDDVCVPQLQ LTASVTGSPL LVGADNVLEL QMDAANE GE GAYEAELAVH LPQGAHYMRA LSNVEGFERL ICNQKKENET RVVLCELGNP MKKNAQIGIA MLVSVGNLEE AGESVSFQ L QIRSKNSQNP NSKIVLLDVP VRAEAQVELR GNSFPASLVV AAEEGEREQN SLDSWGPKVE HTYELHNNGP GTVNGLHLS IHLPGQSQPS DLLYILDIQP QGGLQCFPQP PVNPLKVDWG LPIPSPSPIH PAHHKRDRRQ IFLPEPEQPS RLQDPVLVSC DSAPCTVVQ CDLQEMARGQ RAMVTVLAFL WLPSLYQRPL DQFVLQSHAW FNVSSLPYAV PPLSLPRGEA QVWTQLLRAL E ERAIPIWW VLVGVLGGLL LLTILVLAMW KVGFFKRNRP PLEEDDEEGE UniProtKB: Integrin alpha-IIb |
-分子 #2: Integrin beta-3
分子 | 名称: Integrin beta-3 / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 84.4785 KDa |
配列 | 文字列: GPNICTTRGV SSCQQCLAVS PMCAWCSDEA LPLGSPRCDL KENLLKDNCA PESIEFPVSE ARVLEDRPLS DKGSGDSSQV TQVSPQRIA LRLRPDDSKN FSIQVRQVED YPVDIYYLMD LSYSMKDDLW SIQNLGTKLA TQMRKLTSNL RIGFGAFVDK P VSPYMYIS ...文字列: GPNICTTRGV SSCQQCLAVS PMCAWCSDEA LPLGSPRCDL KENLLKDNCA PESIEFPVSE ARVLEDRPLS DKGSGDSSQV TQVSPQRIA LRLRPDDSKN FSIQVRQVED YPVDIYYLMD LSYSMKDDLW SIQNLGTKLA TQMRKLTSNL RIGFGAFVDK P VSPYMYIS PPEALENPCY DMKTTCLPMF GYKHVLTLTD QVTRFNEEVK KQSVSRNRDA PEGGFDAIMQ ATVCDEKIGW RN DASHLLV FTTDAKTHIA LDGRLAGIVQ PNDGQCHVGS DNHYSASTTM DYPSLGLMTE KLSQKNINLI FAVTENVVNL YQN YSELIP GTTVGVLSMD SSNVLQLIVD AYGKIRSKVE LEVRDLPEEL SLSFNATCLN NEVIPGLKSC MGLKIGDTVS FSIE AKVRG CPQEKEKSFT IKPVGFKDSL IVQVTFDCDC ACQAQAEPNS HRCNNGNGTF ECGVCRCGPG WLGSQCECSE EDYRP SQQD ECSPREGQPV CSQRGECLCG QCVCHSSDFG KITGKYCECD DFSCVRYKGE MCSGHGQCSC GDCLCDSDWT GYYCNC TTR TDTCMSSNGL LCSGRGKCEC GSCVCIQPGS YGDTCEKCPT CPDACTFKKE CVECKKFDRG ALHDENTCNR YCRDEIE SV KELKDTGKDA VNCTYKNEDD CVVRFQYYED SSGKSILYVV EEPECPKGPD ILVVLLSVMG AILLIGLAAL LIWKLLIT I HDRKEFAKFE EERARAKWDT ANNPLYKEAT STFTNITYRG T UniProtKB: Integrin beta-3 |
-分子 #7: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 7 / コピー数: 7 / 式: CA |
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分子量 | 理論値: 40.078 Da |
-分子 #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 8 / コピー数: 6 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-分子 #9: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 9 / コピー数: 2 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-分子 #10: MAGNESIUM ION
分子 | 名称: MAGNESIUM ION / タイプ: ligand / ID: 10 / コピー数: 1 / 式: MG |
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分子量 | 理論値: 24.305 Da |
-分子 #11: water
分子 | 名称: water / タイプ: ligand / ID: 11 / コピー数: 6 / 式: HOH |
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分子量 | 理論値: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | cell |
-試料調製
緩衝液 | pH: 7.4 / 詳細: TBS/1mM CaCl2 |
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / Cs: 0.27 mm / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 81000 |
特殊光学系 | エネルギーフィルター - 名称: GIF Quantum ER / エネルギーフィルター - スリット幅: 10 eV |
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 |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 11947 / 平均電子線量: 50.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |