+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-23436 | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | Oxyntomodulin-bound Glucagon-Like Peptide-1 (GLP-1) Receptor in complex with Gs protein | ||||||||||||||||||
マップデータ | postprocess map | ||||||||||||||||||
試料 |
| ||||||||||||||||||
キーワード | Glucagon-Like Peptide-1 (GLP-1) Receptor / Oxyntomodulin / MEMBRANE PROTEIN | ||||||||||||||||||
機能・相同性 | 機能・相同性情報 Glucagon signaling in metabolic regulation / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (s) signalling events / Glucagon-type ligand receptors / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G alpha (q) signalling events / Synthesis, secretion, and deacylation of Ghrelin / glucagon receptor binding / glucagon-like peptide 1 receptor activity / glucagon receptor activity ...Glucagon signaling in metabolic regulation / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (s) signalling events / Glucagon-type ligand receptors / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G alpha (q) signalling events / Synthesis, secretion, and deacylation of Ghrelin / glucagon receptor binding / glucagon-like peptide 1 receptor activity / glucagon receptor activity / hormone secretion / positive regulation of blood pressure / post-translational protein targeting to membrane, translocation / regulation of heart contraction / response to psychosocial stress / positive regulation of insulin secretion involved in cellular response to glucose stimulus / PKA activation in glucagon signalling / peptide hormone binding / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / cellular response to glucagon stimulus / cAMP-mediated signaling / protein kinase A signaling / negative regulation of blood pressure / adenylate cyclase activator activity / regulation of insulin secretion / trans-Golgi network membrane / response to activity / negative regulation of inflammatory response to antigenic stimulus / bone development / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G protein activity / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / platelet aggregation / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / 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 / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / transmembrane signaling receptor activity / heterotrimeric G-protein complex / sensory perception of smell / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / positive regulation of cold-induced thermogenesis / glucose homeostasis / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) 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 / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / learning or memory / cell surface receptor signaling pathway 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) / Sus scrofa (ブタ) | ||||||||||||||||||
手法 | 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 | Wootten D / Sexton PM | ||||||||||||||||||
資金援助 | オーストラリア, 日本, 5件
| ||||||||||||||||||
引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Dynamics of GLP-1R peptide agonist engagement are correlated with kinetics of G protein activation. 著者: Giuseppe Deganutti / Yi-Lynn Liang / Xin Zhang / Maryam Khoshouei / Lachlan Clydesdale / Matthew J Belousoff / Hari Venugopal / Tin T Truong / Alisa Glukhova / Andrew N Keller / Karen J ...著者: Giuseppe Deganutti / Yi-Lynn Liang / Xin Zhang / Maryam Khoshouei / Lachlan Clydesdale / Matthew J Belousoff / Hari Venugopal / Tin T Truong / Alisa Glukhova / Andrew N Keller / Karen J Gregory / Katie Leach / Arthur Christopoulos / Radostin Danev / Christopher A Reynolds / Peishen Zhao / Patrick M Sexton / Denise Wootten / 要旨: The glucagon-like peptide-1 receptor (GLP-1R) has broad physiological roles and is a validated target for treatment of metabolic disorders. Despite recent advances in GLP-1R structure elucidation, ...The glucagon-like peptide-1 receptor (GLP-1R) has broad physiological roles and is a validated target for treatment of metabolic disorders. Despite recent advances in GLP-1R structure elucidation, detailed mechanistic understanding of how different peptides generate profound differences in G protein-mediated signalling is still lacking. Here we combine cryo-electron microscopy, molecular dynamics simulations, receptor mutagenesis and pharmacological assays, to interrogate the mechanism and consequences of GLP-1R binding to four peptide agonists; glucagon-like peptide-1, oxyntomodulin, exendin-4 and exendin-P5. These data reveal that distinctions in peptide N-terminal interactions and dynamics with the GLP-1R transmembrane domain are reciprocally associated with differences in the allosteric coupling to G proteins. In particular, transient interactions with residues at the base of the binding cavity correlate with enhanced kinetics for G protein activation, providing a rationale for differences in G protein-mediated signalling efficacy from distinct agonists. | ||||||||||||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
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_23436.map.gz | 3.6 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-23436-v30.xml emd-23436.xml | 21.8 KB 21.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_23436_fsc.xml | 6.5 KB | 表示 | FSCデータファイル |
画像 | emd_23436.png | 84.6 KB | ||
マスクデータ | emd_23436_msk_1.map | 22.2 MB | マスクマップ | |
Filedesc metadata | emd-23436.cif.gz | 6.8 KB | ||
その他 | emd_23436_half_map_1.map.gz emd_23436_half_map_2.map.gz | 17 MB 17 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-23436 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23436 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_23436_validation.pdf.gz | 666.5 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_23436_full_validation.pdf.gz | 666.1 KB | 表示 | |
XML形式データ | emd_23436_validation.xml.gz | 12 KB | 表示 | |
CIF形式データ | emd_23436_validation.cif.gz | 16.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23436 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23436 | HTTPS FTP |
-関連構造データ
-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_23436.map.gz / 形式: CCP4 / 大きさ: 22.2 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | postprocess map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-マスク #1
ファイル | emd_23436_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: half map 1
ファイル | emd_23436_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_23436_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 : Oxyntomodulin-GLP-1R-Gs complex
全体 | 名称: Oxyntomodulin-GLP-1R-Gs complex |
---|---|
要素 |
|
-超分子 #1: Oxyntomodulin-GLP-1R-Gs complex
超分子 | 名称: Oxyntomodulin-GLP-1R-Gs complex / 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 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 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: 45.683434 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE ...文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE YQLIDCAQYF LDKIDVIKQA DYVPSDQDLL RCRVLTSGIF ETKFQVDKVN FHMFDVGAQR DERRKWIQCF ND VTAIIFV VASSSYNMVI REDNQTNRLQ AALKLFDSIW NNKWLRDTSV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR YTT PEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCA VDTENIRRVF NDCRDIIQRM HLRQYELL UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-分子 #2: 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: 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: 37.413863 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: QSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: QSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: 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: 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: 6.375332 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFR UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: Nb35
分子 | 名称: Nb35 / 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: Lama glama (ラマ) |
分子量 | 理論値: 13.885439 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSS |
-分子 #5: Pro-glucagon
分子 | 名称: Pro-glucagon / 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: Sus scrofa (ブタ) |
分子量 | 理論値: 4.428878 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: HSQGTFTSDY SKYLDSRRAQ DFVQWLMNTK RNKNNIA UniProtKB: Pro-glucagon |
-分子 #6: Glucagon-like peptide 1 receptor
分子 | 名称: Glucagon-like peptide 1 receptor / タイプ: protein_or_peptide / ID: 6 / 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: 56.748418 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PARPQGATVS LWETVQKWRE YRRQCQRSLT EDPPPATDLF CNRTFDEYAC WPDGEPGSF VNVSCPWYLP WASSVPQGHV YRFCTAEGLW LQKDNSSLPW RDLSECEESK RGERSSPEEQ LLFLYIIYTV G YALSFSAL ...文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PARPQGATVS LWETVQKWRE YRRQCQRSLT EDPPPATDLF CNRTFDEYAC WPDGEPGSF VNVSCPWYLP WASSVPQGHV YRFCTAEGLW LQKDNSSLPW RDLSECEESK RGERSSPEEQ LLFLYIIYTV G YALSFSAL VIASAILLGF RHLHCTRNYI HLNLFASFIL RALSVFIKDA ALKWMYSTAA QQHQWDGLLS YQDSLSCRLV FL LMQYCVA ANYYWLLVEG VYLYTLLAFS VFSEQWIFRL YVSIGWGVPL LFVVPWGIVK YLYEDEGCWT RNSNMNYWLI IRL PILFAI GVNFLIFVRV ICIVVSKLKA NLMCKTDIKC RLAKSTLTLI PLLGTHEVIF AFVMDEHARG TLRFIKLFTE LSFT SFQGL MVAILYCFVN NEVQLEFRKS WERWRLEHLH IQRDSSMKPL KCPTSSLSSG ATAGSSMYTA TCQASCSPAG LEVLF QGPH HHHHHHH UniProtKB: Glucagon-like peptide 1 receptor |
-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
緩衝液 | pH: 7.4 |
---|---|
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
特殊光学系 | 位相板: VOLTA PHASE PLATE 球面収差補正装置: Non-Cs corrected microscope with a Cs=2.7 mm |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均電子線量: 50.0 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 |
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 |