+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-33891 | |||||||||
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タイトル | Cryo-EM structure of the human chemerin receptor 1 complex with the C-terminal nonapeptide of chemerin | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 adipokinetic hormone binding / adipokinetic hormone receptor activity / platelet dense granule lumen / complement receptor activity / regulation of lipid catabolic process / antifungal innate immune response / chemokine receptor activity / embryonic digestive tract development / Class A/1 (Rhodopsin-like receptors) / antifungal humoral response ...adipokinetic hormone binding / adipokinetic hormone receptor activity / platelet dense granule lumen / complement receptor activity / regulation of lipid catabolic process / antifungal innate immune response / chemokine receptor activity / embryonic digestive tract development / Class A/1 (Rhodopsin-like receptors) / antifungal humoral response / complement receptor mediated signaling pathway / positive regulation of chemotaxis / negative regulation of interleukin-12 production / retinoid metabolic process / negative regulation of NF-kappaB transcription factor activity / positive regulation of macrophage chemotaxis / Adenylate cyclase inhibitory pathway / positive regulation of fat cell differentiation / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of calcium-mediated signaling / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / extracellular matrix / skeletal system development / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / response to peptide hormone / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / GDP binding / chemotaxis / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / Platelet degranulation / insulin receptor signaling pathway / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / signaling receptor activity / positive regulation of cold-induced thermogenesis / cell cortex / midbody / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / collagen-containing extracellular matrix / defense response to Gram-negative bacterium / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell differentiation / defense response to Gram-positive bacterium / inflammatory response / cell cycle / positive regulation of protein phosphorylation / immune response 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Vicugna pacos (アルパカ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.81 Å | |||||||||
データ登録者 | Chen G / Liao Q / Ye RD / Wang J | |||||||||
資金援助 | 1件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2023 タイトル: Cryo-EM structure of the human chemerin receptor 1-Gi protein complex bound to the C-terminal nonapeptide of chemerin. 著者: Junlin Wang / Geng Chen / Qiwen Liao / Wenping Lyu / Aijun Liu / Lizhe Zhu / Yang Du / Richard D Ye / 要旨: Chemerin is a processed protein that acts on G protein-coupled receptors (GPCRs) for its chemotactic and adipokine activities. The biologically active chemerin (chemerin 21-157) results from ...Chemerin is a processed protein that acts on G protein-coupled receptors (GPCRs) for its chemotactic and adipokine activities. The biologically active chemerin (chemerin 21-157) results from proteolytic cleavage of prochemerin and uses its C-terminal peptide containing the sequence YFPGQFAFS for receptor activation. Here we report a high-resolution cryo-electron microscopy (cryo-EM) structure of human chemerin receptor 1 (CMKLR1) bound to the C-terminal nonapeptide of chemokine (C9) in complex with Gi proteins. C9 inserts its C terminus into the binding pocket and is stabilized through hydrophobic interactions involving its Y1, F2, F6, and F8, as well as polar interactions between G4, S9, and several amino acids lining the binding pocket of CMKLR1. Microsecond scale molecular dynamics simulations support a balanced force distribution across the whole ligand-receptor interface that enhances thermodynamic stability of the captured binding pose of C9. The C9 interaction with CMKLR1 is drastically different from chemokine recognition by chemokine receptors, which follow a two-site two-step model. In contrast, C9 takes an "S"-shaped pose in the binding pocket of CMKLR1 much like angiotensin II in the AT1 receptor. Our mutagenesis and functional analyses confirmed the cryo-EM structure and key residues in the binding pocket for these interactions. Our findings provide a structural basis for chemerin recognition by CMKLR1 for the established chemotactic and adipokine activities. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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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_33891.map.gz | 64.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-33891-v30.xml emd-33891.xml | 22.3 KB 22.3 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_33891_fsc.xml | 11 KB | 表示 | FSCデータファイル |
画像 | emd_33891.png | 73.7 KB | ||
その他 | emd_33891_half_map_1.map.gz emd_33891_half_map_2.map.gz | 115.9 MB 115.9 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-33891 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33891 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_33891_validation.pdf.gz | 1.1 MB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_33891_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | emd_33891_validation.xml.gz | 19.2 KB | 表示 | |
CIF形式データ | emd_33891_validation.cif.gz | 24.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33891 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33891 | HTTPS FTP |
-関連構造データ
関連構造データ | 7ykdMC 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 (文献) |
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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 |
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「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_33891.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.83 Å | ||||||||||||||||||||
密度 |
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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_33891_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_33891_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 |
-試料の構成要素
+全体 : CMKLR1-Gi -scFv16 complex
+超分子 #1: CMKLR1-Gi -scFv16 complex
+超分子 #2: Retinoic acid receptor responder protein 2
+超分子 #3: Chemerin-like receptor 1, Guanine nucleotide-binding protein G(i)...
+超分子 #4: scFV16
+分子 #1: Retinoic acid receptor responder protein 2
+分子 #2: Chemerin-like receptor 1
+分子 #3: Guanine nucleotide-binding protein G(i) subunit alpha-1
+分子 #4: 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 #6: scFV16
+分子 #7: CHOLESTEROL
-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 |
-試料調製
濃度 | 5 mg/mL |
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緩衝液 | pH: 7.5 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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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: 1.13 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): 2.0 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |