+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7o2w | ||||||
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タイトル | Structure of the C9orf72-SMCR8 complex | ||||||
要素 |
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キーワード | PROTEIN BINDING / Denn domain / Coiled-coil / GTPase-activating protein | ||||||
機能・相同性 | 機能・相同性情報 SUMO is conjugated to E1 (UBA2:SAE1) / Atg1/ULK1 kinase complex / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / late endosome to lysosome transport / SUMOylation of transcription cofactors / regulation of TORC1 signaling ...SUMO is conjugated to E1 (UBA2:SAE1) / Atg1/ULK1 kinase complex / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / late endosome to lysosome transport / SUMOylation of transcription cofactors / regulation of TORC1 signaling / SUMOylation of DNA damage response and repair proteins / regulation of autophagosome assembly / negative regulation of autophagosome assembly / SUMOylation of DNA replication proteins / regulation of actin filament organization / septin ring / guanyl-nucleotide exchange factor complex / SUMOylation of SUMOylation proteins / negative regulation of immune response / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / SUMOylation of RNA binding proteins / axon extension / Flemming body / negative regulation of exocytosis / SUMOylation of chromatin organization proteins / positive regulation of autophagosome maturation / main axon / negative regulation of macroautophagy / detection of maltose stimulus / maltose transport complex / protein kinase inhibitor activity / ubiquitin-like protein ligase binding / carbohydrate transport / positive regulation of macroautophagy / protein sumoylation / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / positive regulation of TOR signaling / autophagosome / axonal growth cone / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / stress granule assembly / ATP-binding cassette (ABC) transporter complex / GTPase activator activity / guanyl-nucleotide exchange factor activity / cell chemotaxis / positive regulation of GTPase activity / negative regulation of protein phosphorylation / condensed nuclear chromosome / regulation of autophagy / cell projection / negative regulation of protein kinase activity / P-body / PML body / small GTPase binding / autophagy / cytoplasmic stress granule / endocytosis / protein tag activity / regulation of protein localization / presynapse / outer membrane-bounded periplasmic space / postsynapse / perikaryon / nuclear membrane / periplasmic space / lysosome / endosome / negative regulation of gene expression / intracellular membrane-bounded organelle / DNA damage response / dendrite / chromatin / protein kinase binding / extracellular space / nucleoplasm / identical protein binding / membrane / nucleus / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Saccharomyces cerevisiae S288c (パン酵母) Homo sapiens (ヒト) Escherichia coli K-12 (大腸菌) | ||||||
手法 | 電子顕微鏡法 / 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. / Schenk, A.D. / Graff-Meyer, A. / Chao, J. / Bhaskar, V. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7o2w.cif.gz | 181.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7o2w.ent.gz | 125.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7o2w.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7o2w_validation.pdf.gz | 397.5 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7o2w_full_validation.pdf.gz | 425.6 KB | 表示 | |
XML形式データ | 7o2w_validation.xml.gz | 23.4 KB | 表示 | |
CIF形式データ | 7o2w_validation.cif.gz | 37.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/o2/7o2w ftp://data.pdbj.org/pub/pdb/validation_reports/o2/7o2w | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 67167.727 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Saccharomyces cerevisiae S288c (パン酵母), (組換発現) Homo sapiens (ヒト) 遺伝子: SMT3, YDR510W, D9719.15, C9orf72 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q12306, UniProt: Q96LT7 |
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#2: タンパク質 | 分子量: 134389.406 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Homo sapiens (ヒト), (組換発現) Escherichia coli K-12 (大腸菌) 遺伝子: SMCR8, malE, b4034, JW3994 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q8TEV9, UniProt: P0AEX9 |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: C9orf72-SMCR8 complex / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 値: 0.201 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 8 |
試料 | 濃度: 0.37 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: SPOT SCAN |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: FEI FALCON III (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 粒子像の数: 284568 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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