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データを開く
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基本情報
| 登録情報 | ![]() | ||||||||||||
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| タイトル | Structure of mouse TLQP21 bound to mouse C3aR in complex with Go | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | G protein coupled receptor / G protein / Membrane protein / Immunite system / SIGNALING PROTEIN | ||||||||||||
| 機能・相同性 | 機能・相同性情報tolerance induction to nonself antigen / complement component C3a binding / carbohydrate homeostasis / complement component C3a receptor activity / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Post-translational protein phosphorylation / Regulation of Complement cascade / complement component C5a receptor activity / Peptide ligand-binding receptors / synaptic signaling via neuropeptide ...tolerance induction to nonself antigen / complement component C3a binding / carbohydrate homeostasis / complement component C3a receptor activity / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Post-translational protein phosphorylation / Regulation of Complement cascade / complement component C5a receptor activity / Peptide ligand-binding receptors / synaptic signaling via neuropeptide / Muscarinic acetylcholine receptors / G protein-coupled acetylcholine receptor activity / G alpha (i) signalling events / positive regulation of glomerular mesangial cell proliferation / neuropeptide hormone activity / mu-type opioid receptor binding / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / vesicle docking involved in exocytosis / corticotropin-releasing hormone receptor 1 binding / complement receptor mediated signaling pathway / positive regulation of neutrophil chemotaxis / G protein-coupled dopamine receptor signaling pathway / insulin secretion / positive regulation of DNA biosynthetic process / positive regulation of macrophage chemotaxis / regulation of locomotion / regulation of heart contraction / response to dietary excess / parallel fiber to Purkinje cell synapse / positive regulation of vascular endothelial growth factor production / regulation of neuronal synaptic plasticity / response to cAMP / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / postsynaptic modulation of chemical synaptic transmission / ovarian follicle development / transport vesicle / Neutrophil degranulation / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / positive regulation of smooth muscle cell proliferation / muscle contraction / response to cold / growth factor activity / generation of precursor metabolites and energy / locomotory behavior / calcium-mediated signaling / hormone activity / negative regulation of insulin secretion / response to insulin / regulation of synaptic plasticity / modulation of chemical synaptic transmission / G protein-coupled receptor activity / GABA-ergic synapse / regulation of blood pressure / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / chemotaxis / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of angiogenesis / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / 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) / 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 / glucose homeostasis / heterotrimeric G-protein complex / G-protein beta-subunit binding / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye 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: 2.88 Å | ||||||||||||
データ登録者 | Banerjee R / Yadav R / Yadav MK / Ganguly M / Mishra S / Dalal A / Gati C / Shukla AK | ||||||||||||
| 資金援助 | 英国, インド, 3件
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引用 | ジャーナル: bioRxiv / 年: 2025タイトル: Molecular fingerprints of a convergent mechanism orchestrating diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptors. 著者: Sudha Mishra / Manish K Yadav / Annu Dalal / Manisankar Ganguly / Ravi Yadav / Kazuhiro Sawada / Divyanshu Tiwari / Nabarun Roy / Nilanjana Banerjee / Jenny N Fung / Jianina Marallag / Cedric ...著者: Sudha Mishra / Manish K Yadav / Annu Dalal / Manisankar Ganguly / Ravi Yadav / Kazuhiro Sawada / Divyanshu Tiwari / Nabarun Roy / Nilanjana Banerjee / Jenny N Fung / Jianina Marallag / Cedric S Cui / Xaria X Li / John D Lee / Calvin Aaron Dsouza / Shirsha Saha / Parishmita Sarma / Ganita Rawat / Houming Zhu / Htet A Khant / Richard J Clark / Fumiya K Sano / Ramanuj Banerjee / Trent M Woodruff / Osamu Nureki / Cornelius Gati / Arun K Shukla / ![]() 要旨: Complement anaphylatoxin receptors (C3aR and C5aR1) are prototypical G protein-coupled receptors (GPCRs) playing crucial physiological roles in innate immunity by combating pathogenic infections and ...Complement anaphylatoxin receptors (C3aR and C5aR1) are prototypical G protein-coupled receptors (GPCRs) playing crucial physiological roles in innate immunity by combating pathogenic infections and orchestrating inflammatory responses. They continue to be important therapeutic targets for multiple disorders including autoimmune diseases, acute and chronic inflammation, and allergy-related conditions. Recent structural coverage has provided important insights into their activation and signaling, however, confounding observations in the literature related to ligand efficacy and functional responses, especially in different model systems, present a major challenge for drug discovery efforts. Here, we systematically and comprehensively profile a broad set of natural and synthetic ligands at C3aR and C5aR1 and discover a previously unanticipated level of functional specialization in terms of species-specific pharmacology and receptor activation. Taking a lead from this, we determine seventeen cryo-EM structures of different ligand-receptor-G-protein complexes and uncover distinct orientation of agonists between the human and mouse receptors despite an overlapping positioning in the orthosteric binding pocket. Combined with extensive mutagenesis and functional assays, these structural snapshots allow us to decode and validate a convergent molecular mechanism involving a "Five-Point-Switch" in these receptors that orchestrates the recognition and efficacy of diverse agonists. We also identify species-specific differences at the level of phosphorylation patterns encoded in the carboxyl-terminus of these receptors and directly visualize their impact on βarr binding and activation using cryo-EM structures. Interestingly, we observe that βarrs engage with the mouse C5aR1 using a variation of previously discovered P-X-P-P phosphorylation motif via a "Sliding-Mechanism" and also exhibit distinct oligomeric state for the human vs. mouse receptors. Taken together, this study elucidates functional specialization at the complement anaphylatoxin receptors and underlying molecular mechanisms, offering a previously lacking framework with direct and immediate implications for the development of novel therapeutics. | ||||||||||||
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構造の表示
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ダウンロードとリンク
-EMDBアーカイブ
| マップデータ | emd_62586.map.gz | 56.1 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-62586-v30.xml emd-62586.xml | 23.9 KB 23.9 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_62586_fsc.xml | 8.4 KB | 表示 | FSCデータファイル |
| 画像 | emd_62586.png | 91 KB | ||
| Filedesc metadata | emd-62586.cif.gz | 7.3 KB | ||
| その他 | emd_62586_half_map_1.map.gz emd_62586_half_map_2.map.gz | 59.4 MB 59.4 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-62586 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-62586 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9kv6MC ![]() 9kugC ![]() 9kutC ![]() 9kv8C ![]() 9kvpC ![]() 9kwgC ![]() 9kwxC ![]() 9kx6C ![]() 9kxsC ![]() 9ky2C ![]() 9kyuC ![]() 9kz2C ![]() 9kz8C ![]() 9kzkC ![]() 9l0hC ![]() 9umjC ![]() 9umrC ![]() 9umxC 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 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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リンク
| EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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| 「今月の分子」の関連する項目 |
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マップ
| ファイル | ダウンロード / ファイル: emd_62586.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 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: 1.294 Å | ||||||||||||||||||||||||||||||||||||
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
| ファイル | emd_62586_half_map_1.map | ||||||||||||
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| 投影像・断面図 |
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| 密度ヒストグラム |
-ハーフマップ: #1
| ファイル | emd_62586_half_map_2.map | ||||||||||||
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| 投影像・断面図 |
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| 密度ヒストグラム |
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試料の構成要素
-全体 : Structure of mouse TLQP21 bound to mouse C3aR in complex with Go
| 全体 | 名称: Structure of mouse TLQP21 bound to mouse C3aR in complex with Go |
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| 要素 |
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-超分子 #1: Structure of mouse TLQP21 bound to mouse C3aR in complex with Go
| 超分子 | 名称: Structure of mouse TLQP21 bound to mouse C3aR in complex with Go タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: VGF-derived peptide TLQP-21
| 分子 | 名称: VGF-derived peptide TLQP-21 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 2.439801 KDa |
| 配列 | 文字列: TLQPPASSRR RHFHHALPPA R UniProtKB: Neurosecretory protein VGF |
-分子 #2: Muscarinic acetylcholine receptor M4,C3a anaphylatoxin chemotacti...
| 分子 | 名称: Muscarinic acetylcholine receptor M4,C3a anaphylatoxin chemotactic receptor タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 59.526031 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSESF DADTNSTDLH SRPLFQPQDI ASMVILGLT CLLGLLGNGL VLWVAGVKMK TTVNTVWFLH LTLADFLCCL SLPFSLAHLI LQGHWPYGLF LCKLIPSIII L NMFASVFL ...文字列: MGKTIIALSY IFCLVFADYK DDDDAANFTP VNGSSGNQSV RLVTSSSLEV LFQGPGSESF DADTNSTDLH SRPLFQPQDI ASMVILGLT CLLGLLGNGL VLWVAGVKMK TTVNTVWFLH LTLADFLCCL SLPFSLAHLI LQGHWPYGLF LCKLIPSIII L NMFASVFL LTAISLDRCL IVHKPIWCQN HRNVRTAFAI CGCVWVVAFV MCVPVFVYRD LFIMDNRSIC RYNFDSSRSY DY WDYVYKL SLPESNSTDN STAQLTGHMN DRSAPSSVQA RDYFWTVTTA LQSQPFLTSP EDSFSLDSAN QQPHYGGKPP NVL TAAVPS GFPVEDRKSN TLNADAFLSA HTELFPTASS GHLYPYDFQG DYVDQFTYDN HVPTPLMAIT ITRLVVGFLV PFFI MVICY SLIVFRMRKT NFTKSRNKTF RVAVAVVTVF FICWTPYHLV GVLLLITDPE SSLGEAVMSW DHMSIALASA NSCFN PFLY ALLGKDFRKK ARQSIKGILE AAFSEELTHS TNCTQDKASS KRNNMSTDV UniProtKB: Muscarinic acetylcholine receptor M4, C3a anaphylatoxin chemotactic receptor |
-分子 #3: Guanine nucleotide-binding protein G(o) subunit alpha
| 分子 | 名称: Guanine nucleotide-binding protein G(o) subunit alpha タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO EC番号: 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 |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 28.193939 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGHHHHHHEN LYFQGTLSAE ERAALERSKA IEKNLKEDGI SAAKDVKLLL LGADNSGKST IVKQMKIIHG GSGGSGGTTG IVETHFTFK NLHFRLFDVG GQRSERKKWI HCFEDVTAII FCVDLSDYDQ VLHEDETTNR MHESLMLFDS ICNNKFFIDT S IILFLNKK ...文字列: MGHHHHHHEN LYFQGTLSAE ERAALERSKA IEKNLKEDGI SAAKDVKLLL LGADNSGKST IVKQMKIIHG GSGGSGGTTG IVETHFTFK NLHFRLFDVG GQRSERKKWI HCFEDVTAII FCVDLSDYDQ VLHEDETTNR MHESLMLFDS ICNNKFFIDT S IILFLNKK DLFGEKIKKS PLTICFPEYT GPNTYEDAAA YIQAQFESKN RSPNKEIYCH MTCATDTNNA QVIFDAVTDI II ANNLRGC GLY UniProtKB: Guanine nucleotide-binding protein G(o) subunit alpha, Guanine nucleotide-binding protein G(o) subunit alpha |
-分子 #4: 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: 4 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 38.534062 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #5: 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: 5 / コピー数: 1 / 光学異性体: LEVO |
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| 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 #6: Antibody fragment - ScFv16
| 分子 | 名称: Antibody fragment - ScFv16 / タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 26.466486 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 K |
-実験情報
-構造解析
| 手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
| 試料の集合状態 | particle |
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試料調製
| 緩衝液 | pH: 7.4 |
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| 凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
| 顕微鏡 | TFS KRIOS |
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| 撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 46.0 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): 3.0 µm / 最小 デフォーカス(公称値): 0.8 µm |
| 試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
| 初期モデル | Chain - Source name: SwissModel / Chain - Initial model type: in silico model |
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| 精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT |
| 得られたモデル | ![]() PDB-9kv6: |
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
英国,
インド, 3件
引用






































































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






































FIELD EMISSION GUN

