+
データを開く
-
基本情報
| 登録情報 | ![]() | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| タイトル | Structure of CD69-bound S1PR1 coupled to heterotrimeric Gi | ||||||||||||
マップデータ | Structure of CD69-bound S1PR1 coupled to heterotrimeric Gi | ||||||||||||
試料 |
| ||||||||||||
キーワード | CD69 / S1PR1 / Sphingosine-1-phosphate / lymphocyte egress / GPCR / Guanine nucleotide-binding protein | ||||||||||||
| 機能・相同性 | 機能・相同性情報negative regulation of T cell migration / cardiac muscle tissue growth involved in heart morphogenesis / blood vessel maturation / sphingolipid binding / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / negative regulation of T-helper 17 cell lineage commitment / endothelial cell differentiation / heart trabecula morphogenesis / regulation of bone mineralization ...negative regulation of T cell migration / cardiac muscle tissue growth involved in heart morphogenesis / blood vessel maturation / sphingolipid binding / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / negative regulation of T-helper 17 cell lineage commitment / endothelial cell differentiation / heart trabecula morphogenesis / regulation of bone mineralization / sphingosine-1-phosphate receptor signaling pathway / leukocyte chemotaxis / positive regulation of positive chemotaxis / regulation of bone resorption / negative regulation of stress fiber assembly / lamellipodium assembly / regulation of metabolic process / transmission of nerve impulse / molecular sequestering activity / regulation of cell adhesion / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / positive regulation of smooth muscle cell proliferation / cellular response to forskolin / regulation of mitotic spindle organization / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / brain development / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / Olfactory Signaling Pathway / Activation of the phototransduction cascade / cellular response to xenobiotic stimulus / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / neuron differentiation / chemotaxis / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / 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 / GDP binding / 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 / transmembrane signaling receptor activity / GPER1 signaling / cell migration / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / presynapse / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / carbohydrate binding / GTPase binding / Ca2+ pathway / actin cytoskeleton organization / fibroblast proliferation / midbody / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cell cortex / angiogenesis 類似検索 - 分子機能 | ||||||||||||
| 生物種 | Homo sapiens (ヒト) / ![]() | ||||||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.15 Å | ||||||||||||
データ登録者 | Chen H / Li X | ||||||||||||
| 資金援助 | 米国, 3件
| ||||||||||||
引用 | ジャーナル: Elife / 年: 2023タイトル: Transmembrane protein CD69 acts as an S1PR1 agonist. 著者: Hongwen Chen / Yu Qin / Marissa Chou / Jason G Cyster / Xiaochun Li / ![]() 要旨: The activation of Sphingosine-1-phosphate receptor 1 (S1PR1) by S1P promotes lymphocyte egress from lymphoid organs, a process critical for immune surveillance and T cell effector activity. Multiple ...The activation of Sphingosine-1-phosphate receptor 1 (S1PR1) by S1P promotes lymphocyte egress from lymphoid organs, a process critical for immune surveillance and T cell effector activity. Multiple drugs that inhibit S1PR1 function are in use clinically for the treatment of autoimmune diseases. Cluster of Differentiation 69 (CD69) is an endogenous negative regulator of lymphocyte egress that interacts with S1PR1 in cis to facilitate internalization and degradation of the receptor. The mechanism by which CD69 causes S1PR1 internalization has been unclear. Moreover, although there are numerous class A GPCR structures determined with different small molecule agonists bound, it remains unknown whether a transmembrane protein per se can act as a class A GPCR agonist. Here, we present the cryo-EM structure of CD69-bound S1PR1 coupled to the heterotrimeric G complex. The transmembrane helix (TM) of one protomer of CD69 homodimer contacts the S1PR1-TM4. This interaction allosterically induces the movement of S1PR1-TMs 5-6, directly activating the receptor to engage the heterotrimeric G. Mutations in key residues at the interface affect the interactions between CD69 and S1PR1, as well as reduce the receptor internalization. Thus, our structural findings along with functional analyses demonstrate that CD69 acts in cis as a protein agonist of S1PR1, thereby promoting G-dependent S1PR1 internalization, loss of S1P gradient sensing, and inhibition of lymphocyte egress. | ||||||||||||
| 履歴 |
|
-
構造の表示
| 添付画像 |
|---|
-
ダウンロードとリンク
-EMDBアーカイブ
| マップデータ | emd_29861.map.gz | 84.6 MB | EMDBマップデータ形式 | |
|---|---|---|---|---|
| ヘッダ (付随情報) | emd-29861-v30.xml emd-29861.xml | 26.6 KB 26.6 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_29861_fsc.xml | 9.5 KB | 表示 | FSCデータファイル |
| 画像 | emd_29861.png | 47.2 KB | ||
| Filedesc metadata | emd-29861.cif.gz | 7.9 KB | ||
| その他 | emd_29861_half_map_1.map.gz emd_29861_half_map_2.map.gz | 71.2 MB 71.3 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-29861 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29861 | HTTPS FTP |
-検証レポート
| 文書・要旨 | emd_29861_validation.pdf.gz | 915.7 KB | 表示 | EMDB検証レポート |
|---|---|---|---|---|
| 文書・詳細版 | emd_29861_full_validation.pdf.gz | 915.3 KB | 表示 | |
| XML形式データ | emd_29861_validation.xml.gz | 17.6 KB | 表示 | |
| CIF形式データ | emd_29861_validation.cif.gz | 22.9 KB | 表示 | |
| アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29861 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29861 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 8g94MC M: このマップから作成された原子モデル 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
| EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
|---|---|
| 「今月の分子」の関連する項目 |
-
マップ
| ファイル | ダウンロード / ファイル: emd_29861.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 注釈 | Structure of CD69-bound S1PR1 coupled to heterotrimeric Gi | ||||||||||||||||||||||||||||||||||||
| 投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
| ボクセルのサイズ | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
| 密度 |
| ||||||||||||||||||||||||||||||||||||
| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
|
-添付データ
-ハーフマップ: Half Map 1
| ファイル | emd_29861_half_map_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 注釈 | Half Map 1 | ||||||||||||
| 投影像・断面図 |
| ||||||||||||
| 密度ヒストグラム |
-ハーフマップ: Half Map 2
| ファイル | emd_29861_half_map_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 注釈 | Half Map 2 | ||||||||||||
| 投影像・断面図 |
| ||||||||||||
| 密度ヒストグラム |
-
試料の構成要素
-全体 : Complex of CD69-bound S1PR1 coupled to heterotrimeric Gi
| 全体 | 名称: Complex of CD69-bound S1PR1 coupled to heterotrimeric Gi |
|---|---|
| 要素 |
|
-超分子 #1: Complex of CD69-bound S1PR1 coupled to heterotrimeric Gi
| 超分子 | 名称: Complex of CD69-bound S1PR1 coupled to heterotrimeric Gi タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 200 KDa |
-分子 #1: Sphingosine 1-phosphate receptor 1
| 分子 | 名称: Sphingosine 1-phosphate receptor 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 40.083781 KDa |
| 組換発現 | 生物種: Homo sapiens (ヒト) |
| 配列 | 文字列: MGPTSVPLVK AHRSSVSDYV NYDIIVRHYN YTGKLNISAD KENSIKLTSV VFILICCFII LENIFVLLTI WKTKKFHRPM YYFIGNLAL SDLLAGVAYT ANLLLSGATT YKLTPAQWFL REGSMFVALS ASVFSLLAIA IERYITMLKM KLHNGSNNFR L FLLISACW ...文字列: MGPTSVPLVK AHRSSVSDYV NYDIIVRHYN YTGKLNISAD KENSIKLTSV VFILICCFII LENIFVLLTI WKTKKFHRPM YYFIGNLAL SDLLAGVAYT ANLLLSGATT YKLTPAQWFL REGSMFVALS ASVFSLLAIA IERYITMLKM KLHNGSNNFR L FLLISACW VISLILGGLP IMGWNCISAL SSCSTVLPLY HKHYILFCTT VFTLLLLSIV ILYCRIYSLV RTRSRRLTFR KN ISKASRS SEKSLALLKT VIIVLSVFIA CWAPLFILLL LDVGCKVKTC DILFRAEYFL VLAVLNSGTN PIIYTLTNKE MRR AFIRIM SCCKCPSGDS AGKFKRPIIA GDYKDDDDK UniProtKB: Sphingosine 1-phosphate receptor 1 |
-分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
| 分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 40.445059 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 37.728152 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: GPGSSGSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...文字列: GPGSSGSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 7.861143 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: scFv16
| 分子 | 名称: scFv16 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 27.784896 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAHHHHHH HH |
-分子 #6: Early activation antigen CD69
| 分子 | 名称: Early activation antigen CD69 / タイプ: protein_or_peptide / ID: 6 / コピー数: 2 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 23.912793 KDa |
| 組換発現 | 生物種: Homo sapiens (ヒト) |
| 配列 | 文字列: MASENCFVAE NSSLHPESGQ ENDATSPHFS TRHEGSFQVP VLCAVMNVVF ITILIIALIA LSVGQYNCPG QYTFSMPSDS HVSSCSEDW VGYQRKCYFI STVKRSWTSA QNACSEHGAT LAVIDSEKDM NFLKRYAGRE EHWVGLKKEP GHPWKWSNGK E FNNWFNVT ...文字列: MASENCFVAE NSSLHPESGQ ENDATSPHFS TRHEGSFQVP VLCAVMNVVF ITILIIALIA LSVGQYNCPG QYTFSMPSDS HVSSCSEDW VGYQRKCYFI STVKRSWTSA QNACSEHGAT LAVIDSEKDM NFLKRYAGRE EHWVGLKKEP GHPWKWSNGK E FNNWFNVT GSDKCVFLKN TEVSSMECEK NLYWICNKPY KGSASWSHPQ FEK UniProtKB: Early activation antigen CD69 |
-実験情報
-構造解析
| 手法 | クライオ電子顕微鏡法 |
|---|---|
解析 | 単粒子再構成法 |
| 試料の集合状態 | particle |
-
試料調製
| 濃度 | 10 mg/mL |
|---|---|
| 緩衝液 | pH: 7.5 |
| グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 400 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY |
| 凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 293 K / 装置: FEI VITROBOT MARK IV |
-
電子顕微鏡法
| 顕微鏡 | FEI TITAN KRIOS |
|---|---|
| 撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 60.0 e/Å2 |
| 電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
| 電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.8 µm |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
ムービー
コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
米国, 3件
引用

































Z (Sec.)
Y (Row.)
X (Col.)





































解析
FIELD EMISSION GUN

