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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Human PIEZO1-MDFIC | |||||||||
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![]() | Human PIEZO1 / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() mechanosensitive monoatomic cation channel activity / positive regulation of viral transcription / cuticular plate / positive regulation of cell-cell adhesion mediated by integrin / detection of mechanical stimulus / positive regulation of integrin activation / Tat protein binding / mechanosensitive monoatomic ion channel activity / stereocilium / regulation of Wnt signaling pathway ...mechanosensitive monoatomic cation channel activity / positive regulation of viral transcription / cuticular plate / positive regulation of cell-cell adhesion mediated by integrin / detection of mechanical stimulus / positive regulation of integrin activation / Tat protein binding / mechanosensitive monoatomic ion channel activity / stereocilium / regulation of Wnt signaling pathway / regulation of JNK cascade / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / negative regulation of protein import into nucleus / positive regulation of myotube differentiation / lamellipodium membrane / monoatomic cation transport / monoatomic cation channel activity / endoplasmic reticulum-Golgi intermediate compartment membrane / cyclin binding / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / regulation of membrane potential / cellular response to mechanical stimulus / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / DNA-binding transcription factor binding / negative regulation of DNA-templated transcription / endoplasmic reticulum membrane / positive regulation of DNA-templated transcription / nucleolus / endoplasmic reticulum / extracellular region / nucleus / plasma membrane / cytoplasm 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: 3.1 Å | |||||||||
![]() | Zhang MF | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of human PIEZO1 and its slow-inactivating channelopathy mutants. 著者: Yuanyue Shan / Xinyi Guo / Mengmeng Zhang / Meiyu Chen / Ying Li / Mingfeng Zhang / Duanqing Pei / ![]() 要旨: PIEZO channels transmit mechanical force signals to cells, allowing them to make critical decisions during development and in pathophysiological conditions. Their fast/slow inactivation modes have ...PIEZO channels transmit mechanical force signals to cells, allowing them to make critical decisions during development and in pathophysiological conditions. Their fast/slow inactivation modes have been implicated in mechanopathologies but remain poorly understood. Here, we report several near-atomic resolution cryo-EM structures of fast-inactivating wild-type human PIEZO1 (hPIEZO1) and its slow-inactivating channelopathy mutants with or without its auxiliary subunit MDFIC. Our results suggest that hPIEZO1 has a more flattened and extended architecture than curved mouse PIEZO1 (mPIEZO1). The multi-lipidated MDFIC subunits insert laterally into the hPIEZO1 pore module like mPIEZO1, resulting in a more curved and extended state. Interestingly, the high-resolution structures suggest that the pore lipids, which directly seal the central hydrophobic pore, may be involved in the rapid inactivation of hPIEZO1. While the severe hereditary erythrocytosis mutant R2456H significantly slows down the inactivation of hPIEZO1, the hPIEZO1-R2456H-MDFIC complex shows a more curved and contracted structure with an inner helix twist due to the broken link between the pore lipid and R2456H. These results suggest that the pore lipids may be involved in the mechanopathological rapid inactivation mechanism of PIEZO channels. | |||||||||
履歴 |
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マップデータ | ![]() | 1.8 GB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 19.3 KB 19.3 KB | 表示 表示 | ![]() |
画像 | ![]() | 25.4 KB | ||
Filedesc metadata | ![]() | 7.4 KB | ||
その他 | ![]() ![]() | 1.8 GB 1.8 GB | ||
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-検証レポート
文書・要旨 | ![]() | 1.2 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.2 MB | 表示 | |
XML形式データ | ![]() | 25.8 KB | 表示 | |
CIF形式データ | ![]() | 30.6 KB | 表示 | |
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-関連構造データ
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EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.57 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
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試料の構成要素
-全体 : human PIEZO1
全体 | 名称: human PIEZO1 |
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要素 |
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-超分子 #1: human PIEZO1
超分子 | 名称: human PIEZO1 / 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: ![]() |
-分子 #1: Piezo-type mechanosensitive ion channel component 1
分子 | 名称: Piezo-type mechanosensitive ion channel component 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 287.094062 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MEPHVLGAVL YWLLLPCALL AACLLRFSGL SLVYLLFLLL LPWFPGPTRC GLQGHTGRLL RALLGLSLLF LVAHLALQIC LHIVPRLDQ LLGPSCSRWE TLSRHIGVTR LDLKDIPNAI RLVAPDLGIL VVSSVCLGIC GRLARNTRQS PHPRELDDDE R DVDASPTA ...文字列: MEPHVLGAVL YWLLLPCALL AACLLRFSGL SLVYLLFLLL LPWFPGPTRC GLQGHTGRLL RALLGLSLLF LVAHLALQIC LHIVPRLDQ LLGPSCSRWE TLSRHIGVTR LDLKDIPNAI RLVAPDLGIL VVSSVCLGIC GRLARNTRQS PHPRELDDDE R DVDASPTA GLQEAATLAP TRRSRLAARF RVTAHWLLVA AGRVLAVTLL ALAGIAHPSA LSSVYLLLFL ALCTWWACHF PI STRGFSR LCVAVGCFGA GHLICLYCYQ MPLAQALLPP AGIWARVLGL KDFVGPTNCS SPHALVLNTG LDWPVYASPG VLL LLCYAT ASLRKLRAYR PSGQRKEAAK GYEARELELA ELDQWPQERE SDQHVVPTAP DTEADNCIVH ELTGQSSVLR RPVR PKRAE PREASPLHSL GHLIMDQSYV CALIAMMVWS ITYHSWLTFV LLLWACLIWT VRSRHQLAML CSPCILLYGM TLCCL RYVW AMDLRPELPT TLGPVSLRQL GLEHTRYPCL DLGAMLLYTL TFWLLLRQFV KEKLLKWAES PAALTEVTVA DTEPTR TQT LLQSLGELVK GVYAKYWIYV CAGMFIVVSF AGRLVVYKIV YMFLFLLCLT LFQVYYSLWR KLLKAFWWLV VAYTMLV LI AVYTFQFQDF PAYWRNLTGF TDEQLGDLGL EQFSVSELFS SILVPGFFLL ACILQLHYFH RPFMQLTDME HVSLPGTR L PRWAHRQDAV SGTPLLREEQ QEHQQQQQEE EEEEEDSRDE GLGVATPHQA TQVPEGAAKW GLVAERLLEL AAGFSDVLS RVQVFLRRLL ELHVFKLVAL YTVWVALKEV SVMNLLLVVL WAFALPYPRF RPMASCLSTV WTCVIIVCKM LYQLKVVNPQ EYSSNCTEP FPNSTNLLPT EISQSLLYRG PVDPANWFGV RKGFPNLGYI QNHLQVLLLL VFEAIVYRRQ EHYRRQHQLA P LPAQAVFA SGTRQQLDQD LLGCLKYFIN FFFYKFGLEI CFLMAVNVIG QRMNFLVTLH GCWLVAILTR RHRQAIARLW PN YCLFLAL FLLYQYLLCL GMPPALCIDY PWRWSRAVPM NSALIKWLYL PDFFRAPNST NLISDFLLLL CASQQWQVFS AER TEEWQR MAGVNTDRLE PLRGEPNPVP NFIHCRSYLD MLKVAVFRYL FWLVLVVVFV TGATRISIFG LGYLLACFYL LLFG TALLQ RDTRARLVLW DCLILYNVTV IISKNMLSLL ACVFVEQMQT GFCWVIQLFS LVCTVKGYYD PKEMMDRDQD CLLPV EEAG IIWDSVCFFF LLLQRRVFLS HYYLHVRADL QATALLASRG FALYNAANLK SIDFHRRIEE KSLAQLKRQM ERIRAK QEK HRQGRVDRSR PQDTLGPKDP GLEPGPDSPG GSSPPRRQWW RPWLDHATVI HSGDYFLFES DSEEEEEAVP EDPRPSA QS AFQLAYQAWV TNAQAVLRRR QQEQEQARQE QAGQLPTGGG PSQEVEPAEG PEEAAAGRSH VVQRVLSTAQ FLWMLGQA L VDELTRWLQE FTRHHGTMSD VLRAERYLLT QELLQGGEVH RGVLDQLYTS QAEATLPGPT EAPNAPSTVS SGLGAEEPL SSMTDDMGSP LSTGYHTRSG SEEAVTDPGE REAGASLYQG LMRTASELLL DRRLRIPELE EAELFAEGQG RALRLLRAVY QCVAAHSEL LCYFIIILNH MVTASAGSLV LPVLVFLWAM LSIPRPSKRF WMTAIVFTEI AVVVKYLFQF GFFPWNSHVV L RRYENKPY FPPRILGLEK TDGYIKYDLV QLMALFFHRS QLLCYGLWDH EEDSPSKEHD KSGEEEQGAE EGPGVPAATT ED HIQVEAR VGPTDGTPEP QVELRPRDTR RISLRFRRRK KEGPARKGAA AIEAEDREEE EGEEEKEAPT GREKRPSRSG GRV RAAGRR LQGFCLSLAQ GTYRPLRRFF HDILHTKYRA ATDVYALMFL ADVVDFIIII FGFWAFGKHS AATDITSSLS DDQV PEAFL VMLLIQFSTM VVDRALYLRK TVLGKLAFQV ALVLAIHLWM FFILPAVTER MFNQNVVAQL WYFVKCIYFA LSAYQ IRCG YPTRILGNFL TKKYNHLNLF LFQGFRLVPF LVELRAVMDW VWTDTTLSLS SWMCVEDIYA NIFIIKCSRE TEKKYP QPK GQKKKKIVKY GMGGLIILFL IAIIWFPLLF MSLVRSVVGV VNQPIDVTVT LKLGGYEPLF TMSAQQPSII PFTAQAY EE LSRQFDPQPL AMQFISQYSP EDIVTAQIEG SSGALWRISP PSRAQMKREL YNGTADITLR FTWNFQRDLA KGGTVEYA N EKHMLALAPN STARRQLASL LEGTSDQSVV IPNLFPKYIR APNGPEANPV KQLQPNEEAD YLGVRIQLRR EQGAGATGF LEWWVIELQE CRTDCNLLPM VIFSDKVSPP SLGFLAGYGI MGLYVSIVLV IGKFVRGFFS EISHSIMFEE LPCVDRILKL CQDIFLVRE TRELELEEEL YAKLIFLYRS PETMIKWTRE KE UniProtKB: Piezo-type mechanosensitive ion channel component 1 |
-分子 #2: MyoD family inhibitor domain-containing protein
分子 | 名称: MyoD family inhibitor domain-containing protein / タイプ: protein_or_peptide / ID: 2 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 25.814113 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MSGAGEALAP GPVGPQRVAE AGGGQLGSTA QGKCDKDNTE KDITQATNSH FTHGEMQDQS IWGNPSDGEL IRTQPQRLPQ LQTSAQVPS GEEIGKIKNG HTGLSNGNGI HHGAKHGSAD NRKLSAPVSQ KMHRKIQSSL SVNSDISKKS KVNAVFSQKT G SSPEDCCV ...文字列: MSGAGEALAP GPVGPQRVAE AGGGQLGSTA QGKCDKDNTE KDITQATNSH FTHGEMQDQS IWGNPSDGEL IRTQPQRLPQ LQTSAQVPS GEEIGKIKNG HTGLSNGNGI HHGAKHGSAD NRKLSAPVSQ KMHRKIQSSL SVNSDISKKS KVNAVFSQKT G SSPEDCCV HCILACLFCE FLTLCNIVLG QASCGICTSE ACCCCCGDEM GDDCNCPCDM DCGIMDACCE SSDCLEICME CC GICFPS UniProtKB: MyoD family inhibitor domain-containing protein |
-分子 #3: DODECANE
分子 | 名称: DODECANE / タイプ: ligand / ID: 3 / コピー数: 15 / 式: D12 |
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分子量 | 理論値: 170.335 Da |
Chemical component information | ![]() ChemComp-D12: |
-分子 #4: (1S)-2-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-1-[(octadeca...
分子 | 名称: (1S)-2-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-1-[(octadecanoyloxy)methyl]ethyl (9Z)-octadec-9-enoate タイプ: ligand / ID: 4 / コピー数: 3 / 式: L9Q |
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分子量 | 理論値: 746.05 Da |
Chemical component information | ![]() ChemComp-L9Q: |
-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
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI MORGAGNI |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 40.0 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 / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.2 µm |