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- PDB-9bw7: Human Vault Cage in complex with PARP4 and NAD+ -

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基本情報

登録情報
データベース: PDB / ID: 9bw7
タイトルHuman Vault Cage in complex with PARP4 and NAD+
要素
  • Major vault protein
  • Protein mono-ADP-ribosyltransferase PARP4
キーワードPROTEIN TRANSPORT / Vault / Vault Cage / MVP / Major Vault Protein / SPFH / PARP4 / Poly(ADP-ribose) Polymerase 4 / MINT / NAD+ / NAD / Poly(ADP-ribose) Polymerase / Ribonucleoprotein / Megadalton complex / TEP1 / vault RNA
機能・相同性
機能・相同性情報


protein activation cascade / Maturation of nucleoprotein / Nicotinate metabolism / ERBB signaling pathway / Maturation of nucleoprotein / NAD+-protein-aspartate ADP-ribosyltransferase activity / NAD+-protein-glutamate ADP-ribosyltransferase activity / NAD+-protein mono-ADP-ribosyltransferase activity / 転移酵素; グリコシル基を移すもの; 五炭糖残基を移すもの / negative regulation of epidermal growth factor receptor signaling pathway ...protein activation cascade / Maturation of nucleoprotein / Nicotinate metabolism / ERBB signaling pathway / Maturation of nucleoprotein / NAD+-protein-aspartate ADP-ribosyltransferase activity / NAD+-protein-glutamate ADP-ribosyltransferase activity / NAD+-protein mono-ADP-ribosyltransferase activity / 転移酵素; グリコシル基を移すもの; 五炭糖残基を移すもの / negative regulation of epidermal growth factor receptor signaling pathway / NAD+ poly-ADP-ribosyltransferase activity / mRNA transport / nuclear pore / nucleotidyltransferase activity / protein modification process / spindle microtubule / protein transport / secretory granule lumen / protein phosphatase binding / ficolin-1-rich granule lumen / cytoskeleton / cell population proliferation / intracellular signal transduction / response to xenobiotic stimulus / ribonucleoprotein complex / inflammatory response / DNA repair / DNA damage response / Neutrophil degranulation / protein kinase binding / perinuclear region of cytoplasm / enzyme binding / DNA binding / extracellular exosome / extracellular region / nucleoplasm / membrane / identical protein binding / nucleus / cytoplasm / cytosol
類似検索 - 分子機能
Protein mono-ADP-ribosyltransferase PARP4 / : / : / PARP4 MVP-ID C-terminal domain / PARP4 WGR-like domain / VIT domain / Vault protein inter-alpha-trypsin domain / VIT domain profile. / Vault protein Inter-alpha-Trypsin domain / Major vault protein, N-terminal ...Protein mono-ADP-ribosyltransferase PARP4 / : / : / PARP4 MVP-ID C-terminal domain / PARP4 WGR-like domain / VIT domain / Vault protein inter-alpha-trypsin domain / VIT domain profile. / Vault protein Inter-alpha-Trypsin domain / Major vault protein, N-terminal / Major vault protein, shoulder domain / Major vault protein / Major vault protein repeat domain 3 / Major vault protein repeat domain 2 / Major vault protein repeat domain 4 / Major vault protein repeat domain / Major vault protein repeat domain superfamily / Major vault protein repeat domain 2 superfamily / Major Vault Protein repeat domain / Shoulder domain / Major Vault Protein repeat domain / Major Vault Protein Repeat domain / Major Vault Protein repeat domain / MVP (vault) repeat profile. / Band 7/SPFH domain superfamily / Poly(ADP-ribose) polymerase, regulatory domain superfamily / Poly(ADP-ribose) polymerase, regulatory domain / PARP alpha-helical domain profile. / von Willebrand factor type A domain / BRCA1 C Terminus (BRCT) domain / Poly(ADP-ribose) polymerase catalytic domain / Poly(ADP-ribose) polymerase, catalytic domain / PARP catalytic domain profile. / breast cancer carboxy-terminal domain / VWFA domain profile. / von Willebrand factor (vWF) type A domain / BRCT domain profile. / BRCT domain / von Willebrand factor, type A / BRCT domain superfamily / von Willebrand factor A-like domain superfamily
類似検索 - ドメイン・相同性
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / Major vault protein / Protein mono-ADP-ribosyltransferase PARP4
類似検索 - 構成要素
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: 2.9 Å
データ登録者Lodwick, J.E. / Zhao, M.
資金援助 米国, 1件
組織認可番号国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35 GM143052 米国
引用
ジャーナル: Nat Commun / 年: 2025
タイトル: Structural insights into the roles of PARP4 and NAD binding in the human vault cage.
著者: Jane E Lodwick / Rong Shen / Satchal Erramilli / Yuan Xie / Karolina Roganowicz / Simone Ritchey / Anthony A Kossiakoff / Minglei Zhao /
要旨: Vault is a massive ribonucleoprotein complex found across Eukaryota. The major vault protein (MVP) oligomerizes into an ovular cage, which contains several minor vault components (MVCs) and is ...Vault is a massive ribonucleoprotein complex found across Eukaryota. The major vault protein (MVP) oligomerizes into an ovular cage, which contains several minor vault components (MVCs) and is thought to transport transiently bound "cargo" molecules. Vertebrate vaults house a poly (ADP-ribose) polymerase (known as PARP4 in humans), which is the only MVC with known enzymatic activity. Despite being discovered decades ago, the molecular basis for PARP4's interaction with MVP remains unclear. In this study, we determined the structure of the human vault cage in complex with PARP4 and its enzymatic substrate NAD. The structures reveal atomic-level details of the protein-binding interface, as well as unexpected binding sites for NAD and related nucleotides within the interior of the vault cage. In addition, proteomics data show that human vaults purified from wild-type and PARP4-depleted cells interact with distinct subsets of proteins. Our results thereby support a model in which PARP4's specific incorporation into the vault cage helps to regulate vault's selection of cargo and its subcellular localization. Further, PARP4's proximity to MVP's NAD-binding sites could support its enzymatic function within the vault.
#1: ジャーナル: bioRxiv / 年: 2024
タイトル: Structural Insights into the Roles of PARP4 and NAD in the Human Vault Cage.
要旨: Vault is a massive ribonucleoprotein complex found across Eukaryota. The major vault protein (MVP) oligomerizes into an ovular cage, which contains several minor vault components (MVCs) and is ...Vault is a massive ribonucleoprotein complex found across Eukaryota. The major vault protein (MVP) oligomerizes into an ovular cage, which contains several minor vault components (MVCs) and is thought to transport transiently bound "cargo" molecules. Vertebrate vaults house a poly (ADP-ribose) polymerase (known as PARP4 in humans), which is the only MVC with known enzymatic activity. Despite being discovered decades ago, the molecular basis for PARP4's interaction with MVP remains unclear. In this study, we determined the structure of the human vault cage in complex with PARP4 and its enzymatic substrate NAD . The structures reveal atomic-level details of the protein-binding interface, as well as unexpected NAD -binding pockets within the interior of the vault cage. In addition, proteomics data show that human vaults purified from wild-type and PARP4-depleted cells interact with distinct subsets of proteins. Our results thereby support a model in which PARP4's specific incorporation into the vault cage helps to regulate vault's selection of cargo and its subcellular localization. Further, PARP4's proximity to MVP's NAD -binding sites could support its enzymatic function within the vault.
#2: ジャーナル: Protein Sci / 年: 2018
タイトル: UCSF ChimeraX: Meeting modern challenges in visualization and analysis.
著者: Thomas D Goddard / Conrad C Huang / Elaine C Meng / Eric F Pettersen / Gregory S Couch / John H Morris / Thomas E Ferrin /
要旨: UCSF ChimeraX is next-generation software for the visualization and analysis of molecular structures, density maps, 3D microscopy, and associated data. It addresses challenges in the size, scope, and ...UCSF ChimeraX is next-generation software for the visualization and analysis of molecular structures, density maps, 3D microscopy, and associated data. It addresses challenges in the size, scope, and disparate types of data attendant with cutting-edge experimental methods, while providing advanced options for high-quality rendering (interactive ambient occlusion, reliable molecular surface calculations, etc.) and professional approaches to software design and distribution. This article highlights some specific advances in the areas of visualization and usability, performance, and extensibility. ChimeraX is free for noncommercial use and is available from http://www.rbvi.ucsf.edu/chimerax/ for Windows, Mac, and Linux.
#3: ジャーナル: Science / 年: 2009
タイトル: The structure of rat liver vault at 3.5 angstrom resolution.
著者: Hideaki Tanaka / Koji Kato / Eiki Yamashita / Tomoyuki Sumizawa / Yong Zhou / Min Yao / Kenji Iwasaki / Masato Yoshimura / Tomitake Tsukihara /
要旨: Vaults are among the largest cytoplasmic ribonucleoprotein particles and are found in numerous eukaryotic species. Roles in multidrug resistance and innate immunity have been suggested, but the ...Vaults are among the largest cytoplasmic ribonucleoprotein particles and are found in numerous eukaryotic species. Roles in multidrug resistance and innate immunity have been suggested, but the cellular function remains unclear. We have determined the x-ray structure of rat liver vault at 3.5 angstrom resolution and show that the cage structure consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains. Each MVP monomer folds into 12 domains: nine structural repeat domains, a shoulder domain, a cap-helix domain, and a cap-ring domain. Interactions between the 42-turn-long cap-helix domains are key to stabilizing the particle. The shoulder domain is structurally similar to a core domain of stomatin, a lipid-raft component in erythrocytes and epithelial cells.
履歴
登録2024年5月20日登録サイト: RCSB / 処理サイト: RCSB
改定 1.02025年2月5日Provider: repository / タイプ: Initial release
改定 1.12025年8月6日Group: Data collection / Database references / カテゴリ: citation / citation_author / em_admin / Item: _em_admin.last_update

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構造の表示

構造ビューア分子:
MolmilJmol/JSmol

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集合体

登録構造単位
A: Major vault protein
B: Protein mono-ADP-ribosyltransferase PARP4
C: Major vault protein
D: Protein mono-ADP-ribosyltransferase PARP4
ヘテロ分子


分子量 (理論値)分子数
合計 (水以外)585,8536
ポリマ－584,5264
非ポリマー1,3272
水00
1
A: Major vault protein
B: Protein mono-ADP-ribosyltransferase PARP4
C: Major vault protein
D: Protein mono-ADP-ribosyltransferase PARP4
ヘテロ分子
x 39


分子量 (理論値)分子数
合計 (水以外)22,848,256234
ポリマ－22,796,509156
非ポリマー51,74778
水0
タイプ名称対称操作数
identity operation1_555x,y,z1
point symmetry operation38
2


  • 登録構造と同一
  • point asymmetric unit
タイプ名称対称操作数
identity operation1_555x,y,z1
対称性点対称性: (シェーンフリース記号: C39 (39回回転対称))

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要素

#1: タンパク質 Major vault protein / MVP / Lung resistance-related protein


分子量: 99452.766 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: MVP, LRP / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: Q14764
#2: タンパク質 Protein mono-ADP-ribosyltransferase PARP4 / 193 kDa vault protein / ADP-ribosyltransferase diphtheria toxin-like 4 / ARTD4 / PARP- ...193 kDa vault protein / ADP-ribosyltransferase diphtheria toxin-like 4 / ARTD4 / PARP-related/IalphaI-related H5/proline-rich / PH5P / Poly [ADP-ribose] polymerase 4 / PARP-4 / Vault poly(ADP-ribose) polymerase / VPARP


分子量: 192810.172 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PARP4, ADPRTL1, KIAA0177, PARPL / 発現宿主: Trichoplusia ni (イラクサキンウワバ)
参照: UniProt: Q9UKK3, 転移酵素; グリコシル基を移すもの; 五炭糖残基を移すもの
#3: 化合物 ChemComp-NAD / NICOTINAMIDE-ADENINE-DINUCLEOTIDE


分子量: 663.425 Da / 分子数: 2 / 由来タイプ: 合成 / 式: C21H27N7O14P2 / タイプ: SUBJECT OF INVESTIGATION / コメント: NAD*YM
研究の焦点であるリガンドがあるかY
Has protein modificationN

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実験情報

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実験

実験手法: 電子顕微鏡法
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

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試料調製

構成要素名称: Ternary complex of NAD+ and human PARP4 bound to oligomerized human MVP
タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT
分子量値: 12.7 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: Trichoplusia ni (イラクサキンウワバ)
緩衝液pH: 8 / 詳細: 50 mM HEPES, 5 mM MgCl2, 5 mM CaCl2, 0.25 mM DTT
緩衝液成分
ID濃度名称式Buffer-ID
150 mMHEPESC8H18N2O4S1
25 mMMagnesium chlorideMgCl21
35 mMCalcium chlorideCaCl21
40.25 mMDTTC4H10O2S21
試料濃度: 1.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES / 詳細: Sample was monodisperse
試料支持詳細: Quantifoil grids with a 2 nm continuous carbon coating were subjected to a 15 s, 5W plasma cleaning program in O2 gas
グリッドの材料: COPPER / グリッドのサイズ: 200 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3
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: 281 K / 詳細: Vitrification carried out under standard conditions

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電子顕微鏡撮影

実験機器
モデル: Titan Krios / 画像提供: FEI Company
顕微鏡モデル: FEI TITAN KRIOS / 詳細: Preliminary grid screening was performed manually.
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 / 倍率（公称値）: 53000 X / 最大 デフォーカス（公称値）: 1700 nm / 最小 デフォーカス（公称値）: 700 nm / Cs: 0.01 mm
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: 45 e/Å2
フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k)
撮影したグリッド数: 1 / 実像数: 5711
詳細: Images were collected in movie mode, with 40 frames per image. Data was collected in SerialEM using a strategy of 3 by 3 + 1 shots per hole.
電子光学装置エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 8 eV
球面収差補正装置: Microscope was modified with a Cs corrector with two hexapole elements

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解析

EMソフトウェア
ID名称バージョンカテゴリ詳細Fitting-ID
1cryoSPARC4.4粒子像選択Manual templates were generated for the first round of picking
2SerialEM4画像取得
4cryoSPARC4.4CTF補正
7Coot0.8.9.2モデルフィッティング1
9cryoSPARC4.4初期オイラー角割当
10cryoSPARC4.4最終オイラー角割当
11cryoSPARC4.4分類
12cryoSPARC4.4３次元再構成cryoSPARC Homogeneous Refinement was performed. The program was instructed to optimize the per-particle defocus and per-exposure-group CTF parameters, fit the anisotropic beam magnification, and apply Ewald sphere correction using the correct curvature sign.
13PHENIX1.12モデル精密化1
14Coot0.8.9.2モデルフィッティング2
15PHENIX1.12モデル精密化2
CTF補正詳細: CTF correction was performed when movies were imported into cryoSPARC Live
タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION
粒子像の選択選択した粒子像数: 174624
対称性点対称性: D39 (2回x39回 2面回転対称)
3次元再構成解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 93859 / アルゴリズム: BACK PROJECTION / 対称性のタイプ: POINT
原子モデル構築
IDプロトコル空間詳細
1FLEXIBLE FITREALThe starting model was the rat homologue of MVP from a previous crystal structure of the vault cage (PDB accession no 4V60). Small molecule coordinates were retrieved from the REFMAC monomer library in COOT. The final model was refined in real space and validated using PHENIX
2FLEXIBLE FITREALPARP4's MINT domain, predicted by AlphaFold2, was used as the starting model. The final model was refined in real space and validated using PHENIX.
原子モデル構築

Chain-ID: A

IDPDB-IDPDB chain-ID 3D fitting-IDAccession codeChain residue rangeInitial refinement model-IDPdb chain residue rangeSource nameタイプ
14v60

4v60

A14v601-84511-845PDBexperimental model
22Q9UKK31562-17242AlphaFoldin silico model

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