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基本情報
登録情報 | データベース: PDB / ID: 7usl | ||||||
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タイトル | Integrin alphaM/beta2 ectodomain in complex with adenylate cyclase toxin RTX751 and M1F5 Fab | ||||||
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![]() | TOXIN / Receptor / Complex / Integrin | ||||||
機能・相同性 | ![]() cellular extravasation / ectodermal cell differentiation / positive regulation of prostaglandin-E synthase activity / response to curcumin / positive regulation of neutrophil degranulation / integrin alphaM-beta2 complex / positive regulation of microglial cell mediated cytotoxicity / response to Gram-positive bacterium / complement component C3b binding / vertebrate eye-specific patterning ...cellular extravasation / ectodermal cell differentiation / positive regulation of prostaglandin-E synthase activity / response to curcumin / positive regulation of neutrophil degranulation / integrin alphaM-beta2 complex / positive regulation of microglial cell mediated cytotoxicity / response to Gram-positive bacterium / complement component C3b binding / vertebrate eye-specific patterning / cytolysis / complement-mediated synapse pruning / Toll Like Receptor 4 (TLR4) Cascade / negative regulation of dopamine metabolic process / leukocyte migration involved in inflammatory response / cell-cell adhesion via plasma-membrane adhesion molecules / complement receptor mediated signaling pathway / heterotypic cell-cell adhesion / integrin complex / cargo receptor activity / cell adhesion mediated by integrin / leukocyte cell-cell adhesion / phagocytosis, engulfment / amyloid-beta clearance / plasma membrane raft / tertiary granule membrane / endothelial cell migration / positive regulation of protein targeting to membrane / Integrin cell surface interactions / specific granule membrane / phagocytosis / response to mechanical stimulus / forebrain development / cell adhesion molecule binding / heat shock protein binding / cell-matrix adhesion / receptor-mediated endocytosis / positive regulation of superoxide anion generation / response to ischemia / integrin-mediated signaling pathway / Cell surface interactions at the vascular wall / microglial cell activation / cell-cell adhesion / positive regulation of angiogenesis / positive regulation of nitric oxide biosynthetic process / integrin binding / response to estradiol / amyloid-beta binding / toxin activity / Interleukin-4 and Interleukin-13 signaling / cell adhesion / membrane raft / external side of plasma membrane / innate immune response / calcium ion binding / Neutrophil degranulation / protein-containing complex binding / cell surface / extracellular space / extracellular exosome / extracellular region / metal ion binding / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() | ||||||
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: 2.7 Å | ||||||
![]() | Goldsmith, J.A. / McLellan, J.S. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis for non-canonical integrin engagement by Bordetella adenylate cyclase toxin. 著者: Jory A Goldsmith / Andrea M DiVenere / Jennifer A Maynard / Jason S McLellan / ![]() 要旨: Integrins are ubiquitous cell-surface heterodimers that are exploited by pathogens and toxins, including leukotoxins that target β integrins on phagocytes. The Bordetella adenylate cyclase toxin ...Integrins are ubiquitous cell-surface heterodimers that are exploited by pathogens and toxins, including leukotoxins that target β integrins on phagocytes. The Bordetella adenylate cyclase toxin (ACT) uses the αβ integrin as a receptor, but the structural basis for integrin binding and neutralization by antibodies is poorly understood. Here, we use cryoelectron microscopy to determine a 2.7 Å resolution structure of an ACT fragment bound to αβ. This structure reveals that ACT interacts with the headpiece and calf-2 of the α subunit in a non-canonical manner specific to bent, inactive αβ. Neutralizing antibody epitopes map to ACT residues involved in α binding, providing the basis for antibody-mediated attachment inhibition. Furthermore, binding to αβ positions the essential ACT acylation sites, which are conserved among toxins exported by type I secretion systems, at the cell membrane. These findings reveal a structural mechanism for integrin-mediated attachment and explain antibody-mediated neutralization of ACT intoxication. | ||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 540.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 405.2 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 805 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 821 KB | 表示 | |
XML形式データ | ![]() | 66.1 KB | 表示 | |
CIF形式データ | ![]() | 100.8 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 26738MC ![]() 7usmC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 3種, 3分子 ABC
#1: タンパク質 | 分子量: 128455.289 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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#2: タンパク質 | 分子量: 80784.938 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
#3: タンパク質 | 分子量: 100286.688 Da / 分子数: 1 / Fragment: C-terminal fragment RTX751, residues 270-1225 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
-抗体 , 2種, 2分子 HL
#4: 抗体 | 分子量: 24665.729 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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#5: 抗体 | 分子量: 23360.854 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
-糖 , 3種, 13分子 ![](data/chem/img/NAG.gif)
#6: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
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#7: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose |
#9: 糖 | ChemComp-NAG / |
-非ポリマー , 1種, 33分子 ![](data/chem/img/CA.gif)
#8: 化合物 | ChemComp-CA / |
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-詳細
研究の焦点であるリガンドがあるか | N |
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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 |
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試料調製
構成要素 | 名称: Ternary complex of integrin alphaM/beta2 ectodomain with adenylate cyclase toxin RTX domain and M1F5 Fab タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 7.5 |
試料 | 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 |
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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 |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2200 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 80 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
ソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 347508 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 57.74 Å2 | ||||||||||||||||||||||||
拘束条件 |
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