+
データを開く
-
基本情報
| 登録情報 | データベース: PDB / ID: 9wey | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| タイトル | Structure of HCMV UL33 in complex with human Gs protein | ||||||||||||||||||||||||||||||||||||
要素 |
| ||||||||||||||||||||||||||||||||||||
キーワード | MEMBRANE PROTEIN / HCMV / viral protein / viral-host interaction / GPCR | ||||||||||||||||||||||||||||||||||||
| 機能・相同性 | 機能・相同性情報adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis ...adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / cellular response to acidic pH / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to glucagon stimulus / intracellular glucose homeostasis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / adenylate cyclase activator activity / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / response to prostaglandin E / bone development / platelet aggregation / cognition / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / positive regulation of insulin secretion / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / sensory perception of smell / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G-protein beta-subunit binding / G alpha (12/13) signalling events / positive regulation of cold-induced thermogenesis / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / G protein activity / fibroblast proliferation / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / GTP binding / protein-containing complex binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||||||||||||||||||||||||||||||||
| 生物種 | Homo sapiens (ヒト)![]() ![]() Human betaherpesvirus 5 (ヘルペスウイルス) | ||||||||||||||||||||||||||||||||||||
| 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: 3.3 Å | ||||||||||||||||||||||||||||||||||||
データ登録者 | Tsutsumi, N. / Suzuki, S. / Nishikawa, K. / Fujiyoshi, Y. | ||||||||||||||||||||||||||||||||||||
| 資金援助 | 日本, 1件
| ||||||||||||||||||||||||||||||||||||
引用 | ジャーナル: Commun Biol / 年: 2026タイトル: Activation of cytomegalovirus-encoded G protein-coupled receptor UL33 by an innate N-terminal peptide. 著者: Anna K Drzazga / Shota Suzuki / Caroline Wouters / Felix Faas / Kouki Nishikawa / Akiko Kamegawa / Yoshinori Fujiyoshi / Mette M Rosenkilde / Naotaka Tsutsumi / ![]() 要旨: Human cytomegalovirus (HCMV) encodes the orphan G protein-coupled receptor (GPCR) UL33, which exhibits constitutive activity that disrupts host G protein signalling, facilitating efficient viral ...Human cytomegalovirus (HCMV) encodes the orphan G protein-coupled receptor (GPCR) UL33, which exhibits constitutive activity that disrupts host G protein signalling, facilitating efficient viral replication and pathogenesis. The cryo-electron microscopy (cryo-EM) structure of UL33 bound to the G subtype of G protein reveals the N-terminal peptide as a tethered ligand reminiscent of the protease-activated receptors and adhesion GPCRs. This self-agonism induces a non-canonical active state that facilitates promiscuous G protein coupling, a plausible viral strategy for fine-tuning host signalling. Structure-guided mutagenesis disrupting key interactions between the N-terminus and its binding pocket abolishes G protein-mediated signalling, confirming the role of the N-terminus as a self-agonist. Our findings elucidate the structural basis for this activation mechanism and highlight the strategies employed by HCMV to hijack host G protein signalling. | ||||||||||||||||||||||||||||||||||||
| 履歴 |
|
-
構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
|---|
-
ダウンロードとリンク
-
ダウンロード
| PDBx/mmCIF形式 | 9wey.cif.gz | 220.6 KB | 表示 | PDBx/mmCIF形式 |
|---|---|---|---|---|
| PDB形式 | pdb9wey.ent.gz | 164.4 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 9wey.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/we/9wey ftp://data.pdbj.org/pub/pdb/validation_reports/we/9wey | HTTPS FTP |
|---|
-関連構造データ
| 関連構造データ | ![]() 65918MC 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 ( |
|---|---|
| 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 | ![]()
|
|---|---|
| 1 |
|
-
要素
| #1: タンパク質 | 分子量: 7729.947 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: GNG2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P59768 |
|---|---|
| #2: 抗体 | 分子量: 15969.623 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: 45568.238 Da / 分子数: 1 Mutation: S54N, G226A, E268A, N271K, K274D, R280K, T284D, I285T, A366S 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAS, GNAS1, GSP / 発現宿主: Homo sapiens (ヒト)参照: UniProt: P63092, 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 |
| #4: タンパク質 | 分子量: 40039.648 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: GNB1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P62873 |
| #5: タンパク質 | 分子量: 68188.695 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: G-protein coupled receptor homolog UL33, LgBit fusion,G-protein coupled receptor homolog UL33, LgBit fusion,G-protein coupled receptor homolog UL33, LgBit fusion,G-protein coupled receptor ...詳細: G-protein coupled receptor homolog UL33, LgBit fusion,G-protein coupled receptor homolog UL33, LgBit fusion,G-protein coupled receptor homolog UL33, LgBit fusion,G-protein coupled receptor homolog UL33, LgBit fusion 由来: (組換発現) ![]() Human betaherpesvirus 5 (ヘルペスウイルス)遺伝子: UL33 発現宿主: ![]() Human betaherpesvirus 5 (ヘルペスウイルス) |
| Has protein modification | Y |
-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: UL33-Gas-Gb1-Gg2-Nb35 / タイプ: COMPLEX 詳細: Cytomegalovirus GPCR UL33 complexed with heterotrimeric Gs protein with dominant negative mutations via HiBit tethering stabilized by nanobody35 Entity ID: all / 由来: RECOMBINANT | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 分子量 | 値: 0.18 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: Homo sapiens (ヒト) | ||||||||||||||||||||||||
| 緩衝液 | pH: 7.2 | ||||||||||||||||||||||||
| 緩衝液成分 |
| ||||||||||||||||||||||||
| 試料 | 濃度: 9 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
| 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
| 顕微鏡 | モデル: JEOL CRYO ARM 300 詳細: The microscope model is the JEOL's "JEM-Z320FHC", a custom-built model of JEOL CRYO ARM 300. |
|---|---|
| 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(補正後): 63291 X / 最大 デフォーカス(公称値): 1200 nm / 最小 デフォーカス(公称値): 600 nm / Cs: 3.4 mm |
| 試料ホルダ | 凍結剤: NITROGEN |
| 撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 2 |
| 電子光学装置 | エネルギーフィルター名称: In-column Omega Filter エネルギーフィルタースリット幅: 20 eV |
-
解析
| EMソフトウェア |
| ||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CTF補正 | 詳細: CryoSPARC patch CTF estimation and global/local CTF refinements タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
| 粒子像の選択 | 選択した粒子像数: 1502019 / 詳細: initial particles that appeared to be protein | ||||||||||||||||||||||||||||||||||||||||
| 対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||||||
| 3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 54507 / アルゴリズム: FOURIER SPACE / 詳細: CryoSPARC non-uniform refinement / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||
| 原子モデル構築 | B value: 106.4 / プロトコル: FLEXIBLE FIT / 空間: REAL | ||||||||||||||||||||||||||||||||||||||||
| 原子モデル構築 | 3D fitting-ID: 1
| ||||||||||||||||||||||||||||||||||||||||
| 精密化 | 最高解像度: 3.3 Å 立体化学のターゲット値: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||||||||||||||||||
| 拘束条件 |
|
ムービー
コントローラー
万見について




Homo sapiens (ヒト)

Human betaherpesvirus 5 (ヘルペスウイルス)
日本, 1件
引用

PDBj






















FIELD EMISSION GUN
