+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8u39 | ||||||
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タイトル | Structure of Human Mitochondrial Chaperonin V72I mutant | ||||||
要素 | 60 kDa heat shock protein, mitochondrial | ||||||
キーワード | CHAPERONE / chaperonin / human mitochondrial mHsp60 / hereditary spastic paraplegia SPG13 / cryo-EM / molecular dynamic simulation | ||||||
機能・相同性 | 機能・相同性情報 coated vesicle / isotype switching to IgG isotypes / lipopolysaccharide receptor complex / TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation / apolipoprotein A-I binding / mitochondrial unfolded protein response / migrasome / high-density lipoprotein particle binding / protein import into mitochondrial intermembrane space / positive regulation of T cell mediated immune response to tumor cell ...coated vesicle / isotype switching to IgG isotypes / lipopolysaccharide receptor complex / TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation / apolipoprotein A-I binding / mitochondrial unfolded protein response / migrasome / high-density lipoprotein particle binding / protein import into mitochondrial intermembrane space / positive regulation of T cell mediated immune response to tumor cell / Mitochondrial protein import / chaperonin ATPase / positive regulation of macrophage activation / cellular response to interleukin-7 / biological process involved in interaction with symbiont / MyD88-dependent toll-like receptor signaling pathway / 'de novo' protein folding / sperm plasma membrane / B cell activation / B cell proliferation / DNA replication origin binding / apoptotic mitochondrial changes / apolipoprotein binding / positive regulation of interleukin-10 production / positive regulation of interferon-alpha production / protein maturation / response to unfolded protein / chaperone-mediated protein complex assembly / clathrin-coated pit / sperm midpiece / T cell activation / positive regulation of interleukin-12 production / response to cold / isomerase activity / secretory granule / Mitochondrial protein degradation / lipopolysaccharide binding / ATP-dependent protein folding chaperone / p53 binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of interleukin-6 production / positive regulation of type II interferon production / double-stranded RNA binding / positive regulation of T cell activation / unfolded protein binding / protein folding / single-stranded DNA binding / protein-folding chaperone binding / protein refolding / early endosome / protein stabilization / mitochondrial inner membrane / mitochondrial matrix / positive regulation of apoptotic process / ubiquitin protein ligase binding / negative regulation of apoptotic process / enzyme binding / cell surface / ATP hydrolysis activity / protein-containing complex / mitochondrion / RNA binding / extracellular space / extracellular exosome / ATP binding / membrane / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
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 / 解像度: 3.4 Å | ||||||
データ登録者 | Chen, L. / Wang, J. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Structure / 年: 2024 タイトル: Cryo-EM structure and molecular dynamic simulations explain the enhanced stability and ATP activity of the pathological chaperonin mutant. 著者: Aiza Syed / Jihang Zhai / Baolin Guo / Yuan Zhao / Joseph Che-Yen Wang / Lingling Chen / 要旨: Chaperonins Hsp60s are required for cellular vitality by assisting protein folding in an ATP-dependent mechanism. Although conserved, the human mitochondrial mHsp60 exhibits molecular characteristics ...Chaperonins Hsp60s are required for cellular vitality by assisting protein folding in an ATP-dependent mechanism. Although conserved, the human mitochondrial mHsp60 exhibits molecular characteristics distinct from the E. coli GroEL, with different conformational assembly and higher subunit association dynamics, suggesting a different mechanism. We previously found that the pathological mutant mHsp60 exhibits enhanced subunit association stability and ATPase activity. To provide structural explanations for the V72I mutational effects, here we determined a cryo-EM structure of mHsp60. Our structural analysis combined with molecular dynamic simulations showed mHsp60 with increased inter-subunit interface, binding free energy, and dissociation force, all contributing to its enhanced subunit association stability. The gate to the nucleotide-binding (NB) site in mHsp60 mimicked the open conformation in the nucleotide-bound state with an additional open channel leading to the NB site, both promoting the mutant's ATPase activity. Our studies highlight the importance of mHsp60's characteristics in its biological function. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8u39.cif.gz | 1.1 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8u39.ent.gz | 954.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8u39.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 | 8u39_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8u39_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 8u39_validation.xml.gz | 110.4 KB | 表示 | |
CIF形式データ | 8u39_validation.cif.gz | 163.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/u3/8u39 ftp://data.pdbj.org/pub/pdb/validation_reports/u3/8u39 | HTTPS FTP |
-関連構造データ
関連構造データ | 41854MC M: このデータのモデリングに利用したマップデータ 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
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 55875.164 Da / 分子数: 7 / 断片: UNP residues 27-550 / 変異: V72I / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: HSPD1 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P10809 |
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-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: Human Mitochondrial Chaperonin V72I Mutant / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 値: 60 kDa/nm / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Escherichia coli (大腸菌) |
緩衝液 | pH: 7.5 |
試料 | 濃度: 7.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R2/2 |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K |
-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: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 800 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 30 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C7 (7回回転対称) | ||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 532348 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL | ||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 7L7S Accession code: 7L7S / Source name: PDB / タイプ: experimental model |