+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-12700 | |||||||||
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タイトル | Structure of the C9orf72-SMCR8 complex | |||||||||
マップデータ | Map of C9orf72-SMCR8 complex | |||||||||
試料 |
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キーワード | Denn domain / Coiled-coil / GTPase-activating protein / PROTEIN BINDING | |||||||||
機能・相同性 | 機能・相同性情報 Atg1/ULK1 kinase complex / SUMO is conjugated to E1 (UBA2:SAE1) / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / late endosome to lysosome transport / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / SUMOylation of transcription cofactors / regulation of TORC1 signaling ...Atg1/ULK1 kinase complex / SUMO is conjugated to E1 (UBA2:SAE1) / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / late endosome to lysosome transport / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / SUMOylation of transcription cofactors / regulation of TORC1 signaling / septin ring / SUMOylation of DNA damage response and repair proteins / negative regulation of autophagosome assembly / regulation of actin filament organization / SUMOylation of DNA replication proteins / guanyl-nucleotide exchange factor complex / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / negative regulation of immune response / regulation of autophagosome assembly / SUMOylation of SUMOylation proteins / SUMOylation of RNA binding proteins / SUMOylation of chromatin organization proteins / Flemming body / presynaptic cytosol / axon extension / negative regulation of exocytosis / positive regulation of autophagosome maturation / main axon / negative regulation of macroautophagy / detection of maltose stimulus / protein kinase inhibitor activity / maltose transport complex / ubiquitin-like protein ligase binding / carbohydrate transport / positive regulation of macroautophagy / maltose binding / protein sumoylation / maltose transport / maltodextrin transmembrane transport / carbohydrate transmembrane transporter activity / positive regulation of TOR signaling / axonal growth cone / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / stress granule assembly / autophagosome / GTPase activator activity / ATP-binding cassette (ABC) transporter complex / cell chemotaxis / negative regulation of protein phosphorylation / guanyl-nucleotide exchange factor activity / positive regulation of GTPase activity / condensed nuclear chromosome / cell projection / regulation of autophagy / P-body / small GTPase binding / autophagy / cytoplasmic stress granule / endocytosis / protein tag activity / regulation of protein localization / presynapse / outer membrane-bounded periplasmic space / nuclear membrane / perikaryon / postsynapse / periplasmic space / lysosome / endosome / intracellular membrane-bounded organelle / negative regulation of gene expression / DNA damage response / dendrite / chromatin / protein kinase binding / extracellular space / nucleoplasm / identical protein binding / membrane / nucleus / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Escherichia coli K-12 (大腸菌) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 | |||||||||
データ登録者 | Noerpel J / Cavadini S | |||||||||
資金援助 | スイス, 1件
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引用 | ジャーナル: PLoS Biol / 年: 2021 タイトル: Structure of the human C9orf72-SMCR8 complex reveals a multivalent protein interaction architecture. 著者: Julia Nörpel / Simone Cavadini / Andreas D Schenk / Alexandra Graff-Meyer / Daniel Hess / Jan Seebacher / Jeffrey A Chao / Varun Bhaskar / 要旨: A major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum disorder is the hexanucleotide G4C2 repeat expansion in the first intron of the C9orf72 gene. ...A major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum disorder is the hexanucleotide G4C2 repeat expansion in the first intron of the C9orf72 gene. Many underlying mechanisms lead to manifestation of disease that include toxic gain-of-function by repeat G4C2 RNAs, dipeptide repeat proteins, and a reduction of the C9orf72 gene product. The C9orf72 protein interacts with SMCR8 and WDR41 to form a trimeric complex and regulates multiple cellular pathways including autophagy. Here, we report the structure of the C9orf72-SMCR8 complex at 3.8 Å resolution using single-particle cryo-electron microscopy (cryo-EM). The structure reveals 2 distinct dimerization interfaces between C9orf72 and SMCR8 that involves an extensive network of interactions. Homology between C9orf72-SMCR8 and Folliculin-Folliculin Interacting Protein 2 (FLCN-FNIP2), a GTPase activating protein (GAP) complex, enabled identification of a key residue within the active site of SMCR8. Further structural analysis suggested that a coiled-coil region within the uDenn domain of SMCR8 could act as an interaction platform for other coiled-coil proteins, and its deletion reduced the interaction of the C9orf72-SMCR8 complex with FIP200 upon starvation. In summary, this study contributes toward our understanding of the biological function of the C9orf72-SMCR8 complex. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_12700.map.gz | 5.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-12700-v30.xml emd-12700.xml | 16.3 KB 16.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_12700.png | 35.7 KB | ||
Filedesc metadata | emd-12700.cif.gz | 6.5 KB | ||
その他 | emd_12700_additional_1.map.gz emd_12700_additional_2.map.gz | 65.3 MB 65.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-12700 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12700 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_12700_validation.pdf.gz | 334.7 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_12700_full_validation.pdf.gz | 334.3 KB | 表示 | |
XML形式データ | emd_12700_validation.xml.gz | 6.2 KB | 表示 | |
CIF形式データ | emd_12700_validation.cif.gz | 7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12700 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12700 | HTTPS FTP |
-関連構造データ
-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_12700.map.gz / 形式: CCP4 / 大きさ: 83.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Map of C9orf72-SMCR8 complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 0.86 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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-添付データ
-追加マップ: Unsharpened map of C9orf72-SMCR8 complex
ファイル | emd_12700_additional_1.map | ||||||||||||
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注釈 | Unsharpened map of C9orf72-SMCR8 complex | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Unsharpened map of C9orf72-SMCR8 complex at 4.3 angstrong
ファイル | emd_12700_additional_2.map | ||||||||||||
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注釈 | Unsharpened map of C9orf72-SMCR8 complex at 4.3 angstrong | ||||||||||||
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 : C9orf72-SMCR8 complex
全体 | 名称: C9orf72-SMCR8 complex |
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要素 |
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-超分子 #1: C9orf72-SMCR8 complex
超分子 | 名称: C9orf72-SMCR8 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: Homo sapiens (ヒト) |
分子量 | 理論値: 201 KDa |
-分子 #1: Ubiquitin-like protein SMT3,Guanine nucleotide exchange C9orf72
分子 | 名称: Ubiquitin-like protein SMT3,Guanine nucleotide exchange C9orf72 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: 67.167727 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MAHHHHHHGS DSEVNQEAKP EVKPEVKPET HINLKVSDGS SEIFFKIKKT TPLRRLMEAF AKRQGKEMDS LRFLYDGIRI QADQTPEDL DMEDNDIIEA HREQISSGLD AAAMSTLCPP PSPAVAKTEI ALSGKSPLLA ATFAYWDNIL GPRVRHIWAP K TEQVLLSD ...文字列: MAHHHHHHGS DSEVNQEAKP EVKPEVKPET HINLKVSDGS SEIFFKIKKT TPLRRLMEAF AKRQGKEMDS LRFLYDGIRI QADQTPEDL DMEDNDIIEA HREQISSGLD AAAMSTLCPP PSPAVAKTEI ALSGKSPLLA ATFAYWDNIL GPRVRHIWAP K TEQVLLSD GEITFLANHT LNGEILRNAE SGAIDVKFFV LSEKGVIIVS LIFDGNWNGD RSTYGLSIIL PQTELSFYLP LH RVCVDRL THIIRKGRIW MHKERQENVQ KIILEGTERM EDQGQSIIPM LTGEVIPVME LLSSMKSHSV PEEIDIADTV LND DDIGDS CHEGFLLNAI SSHLQTCGCS VVVGSSAEKV NKIVRTLCLF LTPAERKCSR LCEAESSFKY ESGLFVQGLL KDST GSFVL PFRQVMYAPY PTTHIDVDVN TVKQMPPCHE HIYNQRRYMR SELTAFWRAT SEEDMAQDTI IYTDESFTPD LNIFQ DVLH RDTLVKAFLD QVFQLKPGLS LRSTFLAQFL LVLHRKALTL IKYIEDDTQK GKKPFKSLRN LKIDLDLTAE GDLNII MAL AEKIKPGLHS FIFGRPFYTS VQERDVLMTF UniProtKB: Ubiquitin-like protein SMT3, Guanine nucleotide exchange factor C9orf72 |
-分子 #2: Guanine nucleotide exchange protein SMCR8,Guanine nucleotide exch...
分子 | 名称: Guanine nucleotide exchange protein SMCR8,Guanine nucleotide exchange protein SMCR8,Maltose/maltodextrin-binding periplasmic protein 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: Escherichia coli K-12 (大腸菌) |
分子量 | 理論値: 134.389406 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MDSAWSHPQF EKGGGSGGGS GGSAWSHPQF EKSAVDLEVL FQGPGMISAP DVVAFTKEEE YEEEPYNEPA LPEEYSVPLF PFASQGANP WSKLSGAKFS RDFILISEFS EQVGPQPLLT IPNDTKVFGT FDLNYFSLRI MSVDYQASFV GHPPGSAYPK L NFVEDSKV ...文字列: MDSAWSHPQF EKGGGSGGGS GGSAWSHPQF EKSAVDLEVL FQGPGMISAP DVVAFTKEEE YEEEPYNEPA LPEEYSVPLF PFASQGANP WSKLSGAKFS RDFILISEFS EQVGPQPLLT IPNDTKVFGT FDLNYFSLRI MSVDYQASFV GHPPGSAYPK L NFVEDSKV VLGDSKEGAF AYVHHLTLYD LEARGFVRPF CMAYISADQH KIMQQFQELS AEFSRASECL KTGNRKAFAG EL EKKLKDL DYTRTVLHTE TEIQKKANDK GFYSSQAIEK ANELASVEKS IIEHQDLLKQ IRSYPHRKLK GHDLCPGEME HIQ DQASQA STTSNPDESA DTDLYTCRPA YTPKLIKAKS TKCFDKKLKT LEELCDTEYF TQTLAQLSHI EHMFRGDLCY LLTS QIDRA LLKQQHITNF LFEDFVEVDD RMVEKQESIP SKPSQDRPPS SSLEECPIPK VLISVGSYKS SVESVLIKME QELGD EEYK DTGSTGSTSG TLEVLFQGPG RQKDQGFRVD FSVENANPSS RDNSCEGFPA YELDPSHLLA SRDISKTSLD NYSDTT SYV SSVASTSSDR IPSAYPAGLS SDRHKKRAGQ NALKFIRQYP FAHPAIYSLL SGRTLVVLGE DEAIVRKLVT ALAIFVP SY GCYAKPVKHW ASSPLHIMDF QKWKLIGLQR VASPAGAGTL HALSRYSRYT SILDLDNKTL RCPLYRGTLV PRLADHRT Q IKRGSTYYLH VQSMLTQLCS KAFLYTFCHH LHLPTHDKET EELVASRQMS FLKLTLGLVN EDVRVVQYLA ELLKLHYMQ ESPGTSHPML RFDYVPSFLY KIGGSGSENL YFQGGTSSGM KIEEGKLVIW INGDKGYNGL AEVGKKFEKD TGIKVTVEHP DKLEEKFPQ VAATGDGPDI IFWAHDRFGG YAQSGLLAEI TPDKAFQDKL YPFTWDAVRY NGKLIAYPIA VEALSLIYNK D LLPNPPKT WEEIPALDKE LKAKGKSALM FNLQEPYFTW PLIAADGGYA FKYENGKYDI KDVGVDNAGA KAGLTFLVDL IK NKHMNAD TDYSIAEAAF NKGETAMTIN GPWAWSNIDT SKVNYGVTVL PTFKGQPSKP FVGVLSAGIN AASPNKELAK EFL ENYLLT DEGLEAVNKD KPLGAVALKS YEEELAKDPR IAATMENAQK GEIMPNIPQM SAFWYAVRTA VINAASGRQT VDEA LKDAQ T UniProtKB: Guanine nucleotide exchange protein SMCR8, Guanine nucleotide exchange protein SMCR8, Maltose/maltodextrin-binding periplasmic protein |
-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 | particle |
-試料調製
濃度 | 0.37 mg/mL |
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緩衝液 | pH: 8 |
凍結 | 凍結剤: ETHANE |
-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: FEI FALCON III (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: FIELD EMISSION GUN |
電子光学系 | 照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: NONE |
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最終 再構成 | 使用した粒子像数: 284568 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |