+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7fdk | ||||||
---|---|---|---|---|---|---|---|
タイトル | SARS-COV-2 Spike RBDMACSp36 binding to mACE2 | ||||||
要素 |
| ||||||
キーワード | VIRAL PROTEIN / SARS-COV-2 Spike / mACE2 | ||||||
機能・相同性 | 機能・相同性情報 Metabolism of Angiotensinogen to Angiotensins / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; 金属プロテアーゼ / angiotensin-mediated drinking behavior / positive regulation of gap junction assembly / tryptophan transport / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy ...Metabolism of Angiotensinogen to Angiotensins / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; 金属プロテアーゼ / angiotensin-mediated drinking behavior / positive regulation of gap junction assembly / tryptophan transport / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / carboxypeptidase activity / positive regulation of cardiac muscle contraction / brush border membrane / negative regulation of smooth muscle cell proliferation / cilium / negative regulation of ERK1 and ERK2 cascade / metallopeptidase activity / virus receptor activity / endopeptidase activity / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / apical plasma membrane / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / cell surface / proteolysis / extracellular space / identical protein binding / membrane / metal ion binding / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | Mus musculus (ハツカネズミ) Severe acute respiratory syndrome coronavirus 2 (ウイルス) | ||||||
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: 3.69 Å | ||||||
データ登録者 | Wang, X. / Cao, L. | ||||||
引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2. 著者: Shihui Sun / Hongjing Gu / Lei Cao / Qi Chen / Qing Ye / Guan Yang / Rui-Ting Li / Hang Fan / Yong-Qiang Deng / Xiaopeng Song / Yini Qi / Min Li / Jun Lan / Rui Feng / Yan Guo / Na Zhu / Si ...著者: Shihui Sun / Hongjing Gu / Lei Cao / Qi Chen / Qing Ye / Guan Yang / Rui-Ting Li / Hang Fan / Yong-Qiang Deng / Xiaopeng Song / Yini Qi / Min Li / Jun Lan / Rui Feng / Yan Guo / Na Zhu / Si Qin / Lei Wang / Yi-Fei Zhang / Chao Zhou / Lingna Zhao / Yuehong Chen / Meng Shen / Yujun Cui / Xiao Yang / Xinquan Wang / Wenjie Tan / Hui Wang / Xiangxi Wang / Cheng-Feng Qin / 要旨: There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory ...There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution. | ||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
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 | 7fdk.cif.gz | 150.5 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb7fdk.ent.gz | 122.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7fdk.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 | 7fdk_validation.pdf.gz | 831.6 KB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 7fdk_full_validation.pdf.gz | 849.3 KB | 表示 | |
XML形式データ | 7fdk_validation.xml.gz | 30.2 KB | 表示 | |
CIF形式データ | 7fdk_validation.cif.gz | 43.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/fd/7fdk ftp://data.pdbj.org/pub/pdb/validation_reports/fd/7fdk | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
#1: タンパク質 | 分子量: 71708.430 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Ace2 / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: Q8R0I0, angiotensin-converting enzyme 2, 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; 金属プロテアーゼ | ||
---|---|---|---|
#2: タンパク質 | 分子量: 24096.109 Da / 分子数: 1 / Mutation: K417N, Q493H, N501Y / 由来タイプ: 組換発現 由来: (組換発現) Severe acute respiratory syndrome coronavirus 2 (ウイルス) 遺伝子: S, 2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 | ||
#3: 糖 | 研究の焦点であるリガンドがあるか | N | |
-実験情報
-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 |
-試料調製
構成要素 | 名称: SARS-COV-2 Spike RBDMACSp36-mACE2 / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
---|---|
由来(天然) | 生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
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 |
-電子顕微鏡撮影
顕微鏡 | モデル: FEI TITAN |
---|---|
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 |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K2 BASE (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.17.1_3660: / 分類: 精密化 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.69 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 162615 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
|