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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of ATP-bound ABCA3 | |||||||||
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機能・相同性 | ![]() positive regulation of protein homooligomerization / lamellar body membrane / Defective ABCA3 causes SMDP3 / Defective ABCA3 causes SMDP3 / alveolar lamellar body membrane / regulation of phosphatidylcholine metabolic process / phosphatidylcholine transfer activity / lamellar body / positive regulation of phospholipid transport / xenobiotic export from cell ...positive regulation of protein homooligomerization / lamellar body membrane / Defective ABCA3 causes SMDP3 / Defective ABCA3 causes SMDP3 / alveolar lamellar body membrane / regulation of phosphatidylcholine metabolic process / phosphatidylcholine transfer activity / lamellar body / positive regulation of phospholipid transport / xenobiotic export from cell / alveolar lamellar body / organelle assembly / phosphatidylcholine flippase activity / ABC transporters in lipid homeostasis / phosphatidylglycerol metabolic process / regulation of lipid biosynthetic process / phosphatidylcholine metabolic process / positive regulation of phospholipid efflux / xenobiotic transmembrane transport / Surfactant metabolism / phospholipid homeostasis / lipid transporter activity / multivesicular body membrane / phospholipid transport / protein metabolic process / ABC-type xenobiotic transporter / P-type phospholipid transporter / xenobiotic transport / surfactant homeostasis / ABC-type xenobiotic transporter activity / lipid transport / ATPase-coupled transmembrane transporter activity / positive regulation of cholesterol efflux / response to glucocorticoid / lung development / cytoplasmic vesicle membrane / late endosome / membrane => GO:0016020 / response to xenobiotic stimulus / lysosomal membrane / intracellular membrane-bounded organelle / ATP hydrolysis activity / extracellular space / ATP binding / 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: 3.3 Å | |||||||||
![]() | Xie T / Zhang ZK / Yue J / Gong X | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Cryo-EM structures of the human surfactant lipid transporter ABCA3. 著者: Tian Xie / Zike Zhang / Jian Yue / Qi Fang / Xin Gong / ![]() 要旨: The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter ABCA3 plays a critical role in pulmonary surfactant biogenesis. Mutations in human ABCA3 have been recognized as the most ...The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter ABCA3 plays a critical role in pulmonary surfactant biogenesis. Mutations in human ABCA3 have been recognized as the most frequent causes of inherited surfactant dysfunction disorders. Despite two decades of research, in vitro biochemical and structural studies of ABCA3 are still lacking. Here, we report the cryo-EM structures of human ABCA3 in two distinct conformations, both at resolution of 3.3 Å. In the absence of ATP, ABCA3 adopts a "lateral-opening" conformation with the lateral surfaces of transmembrane domains (TMDs) exposed to the membrane and features two positively charged cavities within the TMDs as potential substrate binding sites. ATP binding induces pronounced conformational changes, resulting in the collapse of the potential substrate binding cavities. Our results help to rationalize the disease-causing mutations in human ABCA3 and suggest a conserved "lateral access and extrusion" mechanism for both lipid export and import mediated by ABCA transporters. | |||||||||
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 | ![]() | 49.4 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 11.6 KB 11.6 KB | 表示 表示 | ![]() |
画像 | ![]() | 27.9 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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: 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
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試料の構成要素
-全体 : ABCA3
全体 | 名称: ABCA3 |
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要素 |
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-超分子 #1: ABCA3
超分子 | 名称: ABCA3 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() |
-分子 #1: Phospholipid-transporting ATPase ABCA3
分子 | 名称: Phospholipid-transporting ATPase ABCA3 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO / EC番号: P-type phospholipid transporter |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 196.511688 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MADYKDDDDK SGPDEVDASG RMAVLRQLAL LLWKNYTLQK RKVLVTVLEL FLPLLFSGIL IWLRLKIQSE NVPNATIYPG QSIQELPLF FTFPPPGDTW ELAYIPSHSD AAKTVTETVR RALVINMRVR GFPSEKDFED YIRYDNCSSS VLAAVVFEHP F NHSKEPLP ...文字列: MADYKDDDDK SGPDEVDASG RMAVLRQLAL LLWKNYTLQK RKVLVTVLEL FLPLLFSGIL IWLRLKIQSE NVPNATIYPG QSIQELPLF FTFPPPGDTW ELAYIPSHSD AAKTVTETVR RALVINMRVR GFPSEKDFED YIRYDNCSSS VLAAVVFEHP F NHSKEPLP LAVKYHLRFS YTRRNYMWTQ TGSFFLKETE GWHTTSLFPL FPNPGPREPT SPDGGEPGYI REGFLAVQHA VD RAIMEYH ADAATRQLFQ RLTVTIKRFP YPPFIADPFL VAIQYQLPLL LLLSFTYTAL TIARAVVQEK ERRLKEYMRM MGL SSWLHW SAWFLLFFLF LLIAASFMTL LFCVKVKPNV AVLSRSDPSL VLAFLLCFAI STISFSFMVS TFFSKANMAA AFGG FLYFF TYIPYFFVAP RYNWMTLSQK LCSCLLSNVA MAMGAQLIGK FEAKGMGIQW RDLLSPVNVD DDFCFGQVLG MLLLD SVLY GLVTWYMEAV FPGQFGVPQP WYFFIMPSYW CGKPRAVAGK EEEDSDPEKA LRNEYFEAEP EDLVAGIKIK HLSKVF RVG NKDRAAVRDL NLNLYEGQIT VLLGHNGAGK TTTLSMLTGL FPPTSGRAYI SGYEISQDMV QIRKSLGLCP QHDILFD NL TVAEHLYFYA QLKGLSRQKC PEEVKQMLHI IGLEDKWNSR SRFLSGGMRR KLSIGIALIA GSKVLILDQP TSGMDAIS R RAIWDLLQRQ KSDRTIVLTT HFMDEADLLG DRIAIMAKGE LQCCGSSLFL KQKYGAGYHM TLVKEPHCNP EDISQLVHH HVPNATLESS AGAELSFILP RESTHRFEGL FAKLEKKQKE LGIASFGASI TTMEEVFLRV GKLVDSSMDI QAIQLPALQY QHERRASDW AVDSNLCGAM DPSDGIGALI EEERTAVKLN TGLALHCQQF WAMFLKKAAY SWREWKMVAA QVLVPLTCVT L ALLAINYS SELFDDPMLR LTLGEYGRTV VPFSVPGTSQ LGQQLSEHLK DALQAEGQEP REVLGDLEEF LIFRASVEGG GF NERCLVA ASFRDVGERT VVNALFNNQA YHSPATALAV VDNLLFKLLC GPHASIVVSN FPQPRSALQA AKDQFNEGRK GFD IALNLL FAMAFLASTF SILAVSERAV QAKHVQFVSG VHVASFWLSA LLWDLISFLI PSLLLLVVFK AFDVRAFTRD GHMA DTLLL LLLYGWAIIP LMYLMNFFFL GAATAYTRLT IFNILSGIAT FLMVTIMRIP AVKLEELSKT LDHVFLVLPN HCLGM AVSS FYENYETRRY CTSSEVAAHY CKKYNIQYQE NFYAWSAPGV GRFVASMAAS GCAYLILLFL IETNLLQRLR GILCAL RRR RTLTELYTRM PVLPEDQDVA DERTRILAPS PDSLLHTPLI IKELSKVYEQ RVPLLAVDRL SLAVQKGECF GLLGFNG AG KTTTFKMLTG EESLTSGDAF VGGHRISSDV GKVRQRIGYC PQFDALLDHM TGREMLVMYA RLRGIPERHI GACVENTL R GLLLEPHANK LVRTYSGGNK RKLSTGIALI GEPAVIFLDQ PSTGMDPVAR RLLWDTVARA RESGKAIIIT SHSMEECEA LCTRLAIMVQ GQFKCLGSPQ HLKSKFGSGY SLRAKVQSEG QQEALEEFKA FVDLTFPGSV LEDEHQGMVH YHLPGRDLSW AKVFGILEK AKEKYGVDDY SVSQISLEQV FLSFAHLQPP TAEEGRLEGS DEVDAVEGSH HHHHHHHHH |
-分子 #2: ADENOSINE-5'-TRIPHOSPHATE
分子 | 名称: ADENOSINE-5'-TRIPHOSPHATE / タイプ: ligand / ID: 2 / コピー数: 2 / 式: ATP |
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分子量 | 理論値: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-分子 #3: MAGNESIUM ION
分子 | 名称: MAGNESIUM ION / タイプ: ligand / ID: 3 / コピー数: 2 / 式: MG |
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分子量 | 理論値: 24.305 Da |
-分子 #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 4 / コピー数: 2 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-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: 7.5 |
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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) 平均電子線量: 50.0 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 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 80575 |
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初期 角度割当 | タイプ: NOT APPLICABLE |
最終 角度割当 | タイプ: NOT APPLICABLE |