+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7p6s | ||||||||||||
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タイトル | Crystal structure of the FimH-binding decoy module of human glycoprotein 2 (GP2) (crystal form II) | ||||||||||||
要素 | Isoform Alpha of Pancreatic secretory granule membrane major glycoprotein GP2 | ||||||||||||
キーワード | ANTIMICROBIAL PROTEIN / Extracellular matrix / glycoprotein / N-glycan / structural protein / decoy module / D10C domain / D8C sequence / pancreas / intestine / mucosal immunity / FimH / AlphaFold | ||||||||||||
機能・相同性 | 機能・相同性情報 antigen transcytosis by M cells in mucosal-associated lymphoid tissue / zymogen granule membrane / Post-translational modification: synthesis of GPI-anchored proteins / neutrophil migration / antigen binding / endosome / apical plasma membrane / membrane raft / external side of plasma membrane / innate immune response ...antigen transcytosis by M cells in mucosal-associated lymphoid tissue / zymogen granule membrane / Post-translational modification: synthesis of GPI-anchored proteins / neutrophil migration / antigen binding / endosome / apical plasma membrane / membrane raft / external side of plasma membrane / innate immune response / cell surface / extracellular space / extracellular exosome / extracellular region / plasma membrane 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||
手法 | X線回折 / シンクロトロン / 分子置換 / 解像度: 1.35 Å | ||||||||||||
データ登録者 | Stsiapanava, A. / Tunyasuvunakool, K. / Jumper, J. / de Sanctis, D. / Jovine, L. | ||||||||||||
資金援助 | スウェーデン, 3件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2022 タイトル: Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH. 著者: Alena Stsiapanava / Chenrui Xu / Shunsuke Nishio / Ling Han / Nao Yamakawa / Marta Carroni / Kathryn Tunyasuvunakool / John Jumper / Daniele de Sanctis / Bin Wu / Luca Jovine / 要旨: Glycoprotein 2 (GP2) and uromodulin (UMOD) filaments protect against gastrointestinal and urinary tract infections by acting as decoys for bacterial fimbrial lectin FimH. By combining AlphaFold2 ...Glycoprotein 2 (GP2) and uromodulin (UMOD) filaments protect against gastrointestinal and urinary tract infections by acting as decoys for bacterial fimbrial lectin FimH. By combining AlphaFold2 predictions with X-ray crystallography and cryo-EM, we show that these proteins contain a bipartite decoy module whose new fold presents the high-mannose glycan recognized by FimH. The structure rationalizes UMOD mutations associated with kidney diseases and visualizes a key epitope implicated in cast nephropathy. #1: ジャーナル: Biochim.Biophys.Acta / 年: 1978 タイトル: Glycoprotein synthesis in the adult rat pancreas. IV. Subcellular distribution of membrane glycoproteins. 著者: Ronzio, R.A. / Kronquist, K.E. / Lewis, D.S. / MacDonald, R.J. / Mohrlok, S.H. / O'Donnell Jr., J.J. #2: ジャーナル: Biochim.Biophys.Acta / 年: 2000 タイトル: Molecular cloning and sequences of cDNAs encoding alpha (large) and beta (small) isoforms of human pancreatic zymogen granule membrane-associated protein GP2. 著者: Fukuoka, S. #3: ジャーナル: Biochem.Biophys.Res.Commun. / 年: 2004 タイトル: GP2/THP gene family of self-binding, GPI-anchored proteins forms a cluster at chromosome 7F1 region in mouse genome. 著者: Kobayashi, K. / Yanagihara, K. / Ishiguro, K. / Fukuoka, S. #4: ジャーナル: FEBS Lett / 年: 2004 タイトル: Identification and characterization of D8C, a novel domain present in liver-specific LZP, uromodulin and glycoprotein 2, mutated in familial juvenile hyperuricaemic nephropathy. 著者: Huirong Yang / Chaoqun Wu / Shouyuan Zhao / Jinhu Guo / 要旨: Present work reported a novel domain--D8C (domain with conserved eight cysteines in liver-specific ZP domain-containing protein, glycoprotein 2 (GP-2) and uromodulin (UMOD)), present in liver- ...Present work reported a novel domain--D8C (domain with conserved eight cysteines in liver-specific ZP domain-containing protein, glycoprotein 2 (GP-2) and uromodulin (UMOD)), present in liver-specific LZP, UMOD, GP-2 and some uncharacterized proteins, most of which are membrane proteins, extracellular proteins or nuclear membrane proteins. D8C contains eight well-conserved cysteine residues, which were predicted to form four pairs of disulfide bridges. D8C is composed mainly of beta-strands. Mutation in the D8C at Cys217 in human UMOD is associated with familial juvenile hyperuricaemic nephropathy, which might be due to the disruption of the disulfide bridge. Identification of D8C would further the understandings of related proteins. #5: ジャーナル: BMC Gastroenterol / 年: 2009 タイトル: The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli Type 1 fimbriae. 著者: Yu, S. / Lowe, A.W. #6: ジャーナル: Nature / 年: 2009 タイトル: Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response. 著者: Hase, K. / Kawano, K. / Nochi, T. / Pontes, G.S. / Fukuda, S. / Ebisawa, M. / Kadokura, K. / Tobe, T. / Fujimura, Y. / Kawano, S. / Yabashi, A. / Waguri, S. / Nakato, G. / Kimura, S. / ...著者: Hase, K. / Kawano, K. / Nochi, T. / Pontes, G.S. / Fukuda, S. / Ebisawa, M. / Kadokura, K. / Tobe, T. / Fujimura, Y. / Kawano, S. / Yabashi, A. / Waguri, S. / Nakato, G. / Kimura, S. / Murakami, T. / Iimura, M. / Hamura, K. / Fukuoka, S. / Lowe, A.W. / Itoh, K. / Kiyono, H. / Ohno, H. #7: ジャーナル: Gut / 年: 2009 タイトル: Identification of GP2, the major zymogen granule membrane glycoprotein, as the autoantigen of pancreatic antibodies in Crohn's disease. 著者: Roggenbuck, D. / Hausdorf, G. / Martinez-Gamboa, L. / Reinhold, D. / Buttner, T. / Jungblut, P.R. / Porstmann, T. / Laass, M.W. / Henker, J. / Buning, C. / Feist, E. / Conrad, K. #8: ジャーナル: Clin.Chim.Acta / 年: 2012 タイトル: Autoantibodies to GP2, the major zymogen granule membrane glycoprotein, in patients with gluten-sensitive enteropathy: a possible serological trap. 著者: Bonaci-Nikolic, B. / Spuran, M. / Andrejevic, S. / Nikolic, M. #9: ジャーナル: Nature / 年: 2021 タイトル: Highly accurate protein structure prediction with AlphaFold. 著者: John Jumper / Richard Evans / Alexander Pritzel / Tim Green / Michael Figurnov / Olaf Ronneberger / Kathryn Tunyasuvunakool / Russ Bates / Augustin Žídek / Anna Potapenko / Alex Bridgland / ...著者: John Jumper / Richard Evans / Alexander Pritzel / Tim Green / Michael Figurnov / Olaf Ronneberger / Kathryn Tunyasuvunakool / Russ Bates / Augustin Žídek / Anna Potapenko / Alex Bridgland / Clemens Meyer / Simon A A Kohl / Andrew J Ballard / Andrew Cowie / Bernardino Romera-Paredes / Stanislav Nikolov / Rishub Jain / Jonas Adler / Trevor Back / Stig Petersen / David Reiman / Ellen Clancy / Michal Zielinski / Martin Steinegger / Michalina Pacholska / Tamas Berghammer / Sebastian Bodenstein / David Silver / Oriol Vinyals / Andrew W Senior / Koray Kavukcuoglu / Pushmeet Kohli / Demis Hassabis / 要旨: Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort, the structures of around ...Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort, the structures of around 100,000 unique proteins have been determined, but this represents a small fraction of the billions of known protein sequences. Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure. Accurate computational approaches are needed to address this gap and to enable large-scale structural bioinformatics. Predicting the three-dimensional structure that a protein will adopt based solely on its amino acid sequence-the structure prediction component of the 'protein folding problem'-has been an important open research problem for more than 50 years. Despite recent progress, existing methods fall far short of atomic accuracy, especially when no homologous structure is available. Here we provide the first computational method that can regularly predict protein structures with atomic accuracy even in cases in which no similar structure is known. We validated an entirely redesigned version of our neural network-based model, AlphaFold, in the challenging 14th Critical Assessment of protein Structure Prediction (CASP14), demonstrating accuracy competitive with experimental structures in a majority of cases and greatly outperforming other methods. Underpinning the latest version of AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm. | ||||||||||||
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 | 7p6s.cif.gz | 80.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7p6s.ent.gz | 54.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7p6s.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/p6/7p6s ftp://data.pdbj.org/pub/pdb/validation_reports/p6/7p6s | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 17910.852 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GP2 / プラスミド: pLJ6 / 細胞株 (発現宿主): Expi293F GnTI- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P55259 | ||||||
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#2: 糖 | #3: 化合物 | ChemComp-9JE / | #4: 水 | ChemComp-HOH / | 研究の焦点であるリガンドがあるか | Y | |
-実験情報
-実験
実験 | 手法: X線回折 / 使用した結晶の数: 1 |
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-試料調製
結晶 | マシュー密度: 2.42 Å3/Da / 溶媒含有率: 49.27 % / 解説: Plate |
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結晶化 | 温度: 277 K / 手法: 蒸気拡散法, シッティングドロップ法 / pH: 8.5 詳細: 20% (v/v) 1,5-pentanediol, 10% (w/v) PEG 8K, 0.1 M GlyGly/AMPD pH 8.5, 0.5 mM YCl3, 0.5 mM ErCl3, 0.5 mM TbCl3, 0.5 mM YbCl3, 20 mM Na-HEPES pH 7.5, 150 mM NaCl |
-データ収集
回折 | 平均測定温度: 100 K / Serial crystal experiment: N |
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放射光源 | 由来: シンクロトロン / サイト: ESRF / ビームライン: ID30B / 波長: 0.976254 Å |
検出器 | タイプ: DECTRIS PILATUS3 6M / 検出器: PIXEL / 日付: 2021年4月18日 |
放射 | プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 0.976254 Å / 相対比: 1 |
反射 | 解像度: 1.35→49.12 Å / Num. obs: 38991 / % possible obs: 99.7 % / 冗長度: 6 % / Biso Wilson estimate: 13.25 Å2 / CC1/2: 1 / CC star: 1 / Rmerge(I) obs: 0.153 / Rpim(I) all: 0.067 / Rrim(I) all: 0.167 / Net I/σ(I): 7 |
反射 シェル | 解像度: 1.35→1.39 Å / 冗長度: 4.7 % / Rmerge(I) obs: 2.318 / Mean I/σ(I) obs: 0.7 / Num. unique obs: 2960 / CC1/2: 0.4 / CC star: 0.75 / Rpim(I) all: 1.18 / Rrim(I) all: 2.612 / % possible all: 98.2 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 分子置換 開始モデル: Partially refined model of crystal form I of the same protein (PDB D_1292117104) 解像度: 1.35→49.12 Å / SU ML: 0.1991 / 交差検証法: FREE R-VALUE / σ(F): 1.34 / 位相誤差: 27.0674 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å / 溶媒モデル: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 18.48 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 1.35→49.12 Å
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拘束条件 |
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LS精密化 シェル |
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