+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-32861 | ||||||||||||
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タイトル | Cryo-EM structure of the human formyl peptide receptor 2 in complex with fhumanin and Gi2 | ||||||||||||
マップデータ | |||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 negative regulation of interleukin-18 production / N-formyl peptide receptor activity / complement receptor activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / immune response-regulating cell surface receptor signaling pathway / receptor antagonist activity / negative regulation of neuroinflammatory response / scavenger receptor binding / negative regulation of interleukin-1 production / negative regulation of NLRP3 inflammasome complex assembly ...negative regulation of interleukin-18 production / N-formyl peptide receptor activity / complement receptor activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / immune response-regulating cell surface receptor signaling pathway / receptor antagonist activity / negative regulation of neuroinflammatory response / scavenger receptor binding / negative regulation of interleukin-1 production / negative regulation of NLRP3 inflammasome complex assembly / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / complement receptor mediated signaling pathway / negative regulation of adenylate cyclase activity / negative regulation of execution phase of apoptosis / positive regulation of neural precursor cell proliferation / positive regulation of innate immune response / Formyl peptide receptors bind formyl peptides and many other ligands / negative regulation of amyloid fibril formation / positive regulation of monocyte chemotaxis / leukocyte chemotaxis / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / cargo receptor activity / negative regulation of response to oxidative stress / positive chemotaxis / neuronal dense core vesicle / regulation of calcium ion transport / tertiary granule membrane / negative regulation of apoptotic signaling pathway / ficolin-1-rich granule membrane / sperm flagellum / Adenylate cyclase inhibitory pathway / specific granule membrane / supramolecular fiber organization / positive regulation of insulin receptor signaling pathway / positive regulation of phagocytosis / sperm midpiece / positive regulation of vascular associated smooth muscle cell proliferation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to nutrient / receptor-mediated endocytosis / positive regulation of superoxide anion generation / mitochondrion organization / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / astrocyte activation / electron transport chain / microglial cell activation / calcium-mediated signaling / cell cycle / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / 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 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / negative regulation of inflammatory response / 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 / cellular response to amyloid-beta / 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 / 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) / GTPase binding / cell-cell signaling / retina development in camera-type eye / Ca2+ pathway 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: 2.8 Å | ||||||||||||
データ登録者 | Zhu Y / Lin X / Zong X / Han S / Zhao Q / Wu B | ||||||||||||
資金援助 | 中国, 3件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Structural basis of FPR2 in recognition of Aβ and neuroprotection by humanin. 著者: Ya Zhu / Xiaowen Lin / Xin Zong / Shuo Han / Mu Wang / Yuxuan Su / Limin Ma / Xiaojing Chu / Cuiying Yi / Qiang Zhao / Beili Wu / 要旨: Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of the β amyloid peptide Aβ and serves as a receptor for humanin, a peptide that protects neuronal cells from damage ...Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of the β amyloid peptide Aβ and serves as a receptor for humanin, a peptide that protects neuronal cells from damage by Aβ, implying its involvement in the pathogenesis of Alzheimer's disease (AD). However, the interaction pattern between FPR2 and Aβ or humanin remains unknown. Here we report the structures of FPR2 bound to G and Aβ or N-formyl humanin (fHN). Combined with functional data, the structures reveal two critical regions that govern recognition and activity of Aβ and fHN, including a polar binding cavity within the receptor helical bundle and a hydrophobic binding groove in the extracellular region. In addition, the structures of FPR2 and FPR1 in complex with different formyl peptides were determined, providing insights into ligand recognition and selectivity of the FPR family. These findings uncover key factors that define the functionality of FPR2 in AD and other inflammatory diseases and would enable drug development. | ||||||||||||
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_32861.map.gz | 59.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-32861-v30.xml emd-32861.xml | 14.9 KB 14.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_32861.png | 27.2 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-32861 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32861 | HTTPS FTP |
-関連構造データ
-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_32861.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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ボクセルのサイズ | X=Y=Z: 1.045 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
-試料の構成要素
-全体 : Formyl peptide receptor 2 in complex with fhumanin and Gi2
全体 | 名称: Formyl peptide receptor 2 in complex with fhumanin and Gi2 |
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要素 |
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-超分子 #1: Formyl peptide receptor 2 in complex with fhumanin and Gi2
超分子 | 名称: Formyl peptide receptor 2 in complex with fhumanin and Gi2 タイプ: complex / キメラ: Yes / 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) |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
-分子 #1: Humanin
分子 | 名称: Humanin / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 2.719275 KDa |
配列 | 文字列: (FME)APRGFSCLL LLTSEIDLPV KRRA |
-分子 #2: Soluble cytochrome b562,N-formyl peptide receptor 2
分子 | 名称: Soluble cytochrome b562,N-formyl peptide receptor 2 / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 56.710328 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: GAPADLEDNW ETLNDNLKVI EKADNAAQVK DALTKMRAAA LDAQKATPPK LEDKSPDSPE MKDFRHGFDI LVGQIDDALK LANEGKVKE AQAAAEQLKT TRNAYIQKYL GSGSENLYFQ SETNFSTPLN EYEEVSYESA GYTVLRILPL VVLGVTFVLG V LGNGLVIW ...文字列: GAPADLEDNW ETLNDNLKVI EKADNAAQVK DALTKMRAAA LDAQKATPPK LEDKSPDSPE MKDFRHGFDI LVGQIDDALK LANEGKVKE AQAAAEQLKT TRNAYIQKYL GSGSENLYFQ SETNFSTPLN EYEEVSYESA GYTVLRILPL VVLGVTFVLG V LGNGLVIW VAGFRMTRTV TTICYLNLAL ADFSFTATLP FLIVSMAMGE KWPFGWFLCK LIHIVVDINL FGSVFLIGFI AL DRCICVL HPVWAQNHRT VSLAMKVIVG PWILALVLTL PVFLFLTTVT IPNGDTYCTF NFASWGGTPE ERLKVAITML TAR GIIRFV IGFLLPMSIV AICYGLIAAK IHKKGMIKSS RPLRVLTAVV ASFFICWFPF QLVALLGTVW LKEMLFYGKY KIID ILVNP TSSLAFFNSC LNPMLYVFVG QDFRERLIHS LPTSLERALS EDSAPTNDTA ANSASPPAET EFLEVLFQGP GSWSH PQFE KGSGAGASAG SWSHPQFEKG SDYKDDDDK |
-分子 #3: Guanine nucleotide-binding protein G(i) subunit alpha-2
分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-2 タイプ: protein_or_peptide / ID: 3 / 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: 40.502863 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEDG YSEEECRQYR AVVYSNTIQS IMAIVKAMG NLQIDFADPS RADDARQLFA LSCTAEEQGV LPDDLSGVIR RLWADHGVQA CFGRSREYQL NDSAAYYLND L ERIAQSDY ...文字列: MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEDG YSEEECRQYR AVVYSNTIQS IMAIVKAMG NLQIDFADPS RADDARQLFA LSCTAEEQGV LPDDLSGVIR RLWADHGVQA CFGRSREYQL NDSAAYYLND L ERIAQSDY IPTQQDVLRT RVKTTGIVET HFTFKDLHFK MFDVGAQRSE RKKWIHCFEG VTAIIFCVAL SAYDLVLAED EE MNRMHAS MKLFDSICNN KWFTDTSIIL FLNKKDLFEE KITHSPLTIC FPEYTGANKY DEAASYIQSK FEDLNKRKDT KEI YTHFTC STDTKNVQFV FDAVTDVIIK NNLKDCGLF |
-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: 38.744371 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWN |
-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: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-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
緩衝液 | pH: 7.5 |
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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: 2.1875 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: SPOT SCAN / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1.5 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 |
-画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 1398841 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |