+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-38128 | |||||||||
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タイトル | Structure of human SCMC ternary complex | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | oocyte / subcortical / complex / CYTOSOLIC PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 embryonic process involved in female pregnancy / subcortical maternal complex / regulation of localization / endoplasmic reticulum localization / establishment of organelle localization / cortical granule exocytosis / establishment or maintenance of apical/basal cell polarity / SUMO is conjugated to E1 (UBA2:SAE1) / cortical granule / SUMOylation of nuclear envelope proteins ...embryonic process involved in female pregnancy / subcortical maternal complex / regulation of localization / endoplasmic reticulum localization / establishment of organelle localization / cortical granule exocytosis / establishment or maintenance of apical/basal cell polarity / SUMO is conjugated to E1 (UBA2:SAE1) / cortical granule / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / positive regulation of meiotic nuclear division / positive regulation of embryonic development / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / SUMOylation of transcription cofactors / regulation of establishment of protein localization / establishment of spindle localization / septin ring / mitochondrion localization / SUMOylation of DNA damage response and repair proteins / SUMOylation of DNA replication proteins / embryonic pattern specification / SUMOylation of SUMOylation proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / SUMOylation of RNA binding proteins / SUMOylation of chromatin organization proteins / positive regulation of double-strand break repair / detection of maltose stimulus / maltose transport complex / replication fork processing / ubiquitin-like protein ligase binding / regulation of cell division / maltose binding / carbohydrate transport / exocytosis / maltose transport / maltodextrin transmembrane transport / protein sumoylation / carbohydrate transmembrane transporter activity / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / positive regulation of double-strand break repair via homologous recombination / tubulin binding / ATP-binding cassette (ABC) transporter complex / cell chemotaxis / condensed nuclear chromosome / actin filament organization / negative regulation of canonical Wnt signaling pathway / transcription corepressor activity / protein tag activity / regulation of protein localization / outer membrane-bounded periplasmic space / cell cortex / regulation of inflammatory response / transcription regulator complex / periplasmic space / intracellular membrane-bounded organelle / DNA damage response / nucleolus / Golgi apparatus / negative regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / RNA binding / ATP binding / identical protein binding / membrane / nucleus / cytosol / cytoplasm 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: 3.01 Å | |||||||||
データ登録者 | Chi P / Ou G / Liu S / Lu Y / Li JH / Li JL / Wang X / Deng D | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2024 タイトル: Cryo-EM structure of the human subcortical maternal complex and the associated discovery of infertility-associated variants. 著者: Pengliang Chi / Guojin Ou / Sibei Liu / Qianhong Ma / Yuechao Lu / Jinhong Li / Jialu Li / Qianqian Qi / Zhuo Han / Zihan Zhang / Qingting Liu / Li Guo / Jing Chen / Xiang Wang / Wei Huang / Lei Li / Dong Deng / 要旨: The functionally conserved subcortical maternal complex (SCMC) is essential for early embryonic development in mammals. Reproductive disorders caused by pathogenic variants in NLRP5, TLE6 and OOEP, ...The functionally conserved subcortical maternal complex (SCMC) is essential for early embryonic development in mammals. Reproductive disorders caused by pathogenic variants in NLRP5, TLE6 and OOEP, three core components of the SCMC, have attracted much attention over the past several years. Evaluating the pathogenicity of a missense variant in the SCMC is limited by the lack of information on its structure, although we recently solved the structure of the mouse SCMC and proposed that reproductive disorders caused by pathogenic variants are related to the destabilization of the SCMC core complex. Here we report the cryogenic electron microscopy structure of the human SCMC and uncover that the pyrin domain of NLRP5 is essential for the stability of SCMC. By combining prediction of SCMC stability and in vitro reconstitution, we provide a method for identifying deleterious variants, and we successfully identify a new pathogenic variant of TLE6 (p.A396T). Thus, on the basis of the structure of the human SCMC, we offer a strategy for the diagnosis of reproductive disorders and the discovery of new infertility-associated variants. | |||||||||
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_38128.map.gz | 59.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-38128-v30.xml emd-38128.xml | 17.9 KB 17.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_38128.png | 46.9 KB | ||
マスクデータ | emd_38128_msk_1.map | 64 MB | マスクマップ | |
Filedesc metadata | emd-38128.cif.gz | 6.9 KB | ||
その他 | emd_38128_half_map_1.map.gz emd_38128_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-38128 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38128 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_38128_validation.pdf.gz | 943.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_38128_full_validation.pdf.gz | 942.9 KB | 表示 | |
XML形式データ | emd_38128_validation.xml.gz | 12.3 KB | 表示 | |
CIF形式データ | emd_38128_validation.cif.gz | 14.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38128 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38128 | HTTPS FTP |
-関連構造データ
関連構造データ | 8x7vMC 8x7wC 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_38128.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: 1.1 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
-マスク #1
ファイル | emd_38128_msk_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: #2
ファイル | emd_38128_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_38128_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 : human SCMC ternary complex
全体 | 名称: human SCMC ternary complex |
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要素 |
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-超分子 #1: human SCMC ternary complex
超分子 | 名称: human SCMC ternary complex / 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: Maltose/maltodextrin-binding periplasmic protein,NACHT, LRR and P...
分子 | 名称: Maltose/maltodextrin-binding periplasmic protein,NACHT, LRR and PYD domains-containing protein 5 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: 171.393734 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MDYKDDDDKG DYKDDDDKGS MKIEEGKLVI WINGDKGYNG LAEVGKKFEK DTGIKVTVEH PDKLEEKFPQ VAATGDGPDI IFWAHDRFG GYAQSGLLAE ITPDKAFQDK LYPFTWDAVR YNGKLIAYPI AVEALSLIYN KDLLPNPPKT WEEIPALDKE L KAKGKSAL ...文字列: MDYKDDDDKG DYKDDDDKGS MKIEEGKLVI WINGDKGYNG LAEVGKKFEK DTGIKVTVEH PDKLEEKFPQ VAATGDGPDI IFWAHDRFG GYAQSGLLAE ITPDKAFQDK LYPFTWDAVR YNGKLIAYPI AVEALSLIYN KDLLPNPPKT WEEIPALDKE L KAKGKSAL MFNLQEPYFT WPLIAADGGY AFKYENGKYD IKDVGVDNAG AKAGLTFLVD LIKNKHMNAD TDYSIAEAAF NK GETAMTI NGPWAWSNID TSKVNYGVTV LPTFKGQPSK PFVGVLSAGI NAASPNKELA KEFLENYLLT DEGLEAVNKD KPL GAVALK SYEEELAKDP RIAATMENAQ KGEIMPNIPQ MSAFWYAVRT AVINAASGRQ TVDEALKDAQ TLTFSSYGLQ WCLY ELDKE EFQTFKELLK KKSSESTTCS IPQFEIENAN VECLALLLHE YYGASLAWAT SISIFENMNL RTLSEKARDD MKRHS PEDP EATMTDQGPS KEKVPGISQA VQQDSATAAE TKEQEISQAM EQEGATAAET EEQEISQAME QEGATAAETE EQGHGG DTW DYKSHVMTKF AEEEDVRRSF ENTAADWPEM QTLAGAFDSD RWGFRPRTVV LHGKSGIGKS ALARRIVLCW AQGGLYQ GM FSYVFFLPVR EMQRKKESSV TEFISREWPD SQAPVTEIMS RPERLLFIID GFDDLGSVLN NDTKLCKDWA EKQPPFTL I RSLLRKVLLP ESFLIVTVRD VGTEKLKSEV VSPRYLLVRG ISGEQRIHLL LERGIGEHQK TQGLRAIMNN RELLDQCQV PAVGSLICVA LQLQDVVGES VAPFNQTLTG LHAAFVFHQL TPRGVVRRCL NLEERVVLKR FCRMAVEGVW NRKSVFDGDD LMVQGLGES ELRALFHMNI LLPDSHCEEY YTFFHLSLQD FCAALYYVLE GLEIEPALCP LYVEKTKRSM ELKQAGFHIH S LWMKRFLF GLVSEDVRRP LEVLLGCPVP LGVKQKLLHW VSLLGQQPNA TTPGDTLDAF HCLFETQDKE FVRLALNSFQ EV WLPINQN LDLIASSFCL QHCPYLRKIR VDVKGIFPRD ESAEACPVVP LWMRDKTLIE EQWEDFCSML GTHPHLRQLD LGS SILTER AMKTLCAKLR HPTCKIQTLM FRNAQITPGV QHLWRIVMAN RNLRSLNLGG THLKEEDVRM ACEALKHPKC LLES LRLDC CGLTHACYLK ISQILTTSPS LKSLSLAGNK VTDQGVMPLS DALRVSQCAL QKLILEDCGI TATGCQSLAS ALVSN RSLT HLCLSNNSLG NEGVNLLCRS MRLPHCSLQR LMLNQCHLDT AGCGFLALAL MGNSWLTHLS LSMNPVEDNG VKLLCE VMR EPSCHLQDLE LVKCHLTAAC CESLSCVISR SRHLKSLDLT DNALGDGGVA ALCEGLKQKN SVLARLGLKA CGLTSDC CE ALSLALSCNR HLTSLNLVQN NFSPKGMMKL CSAFACPTSN LQIIGLWKWQ YPVQIRKLLE EVQLLKPRVV IDGSWHSF D EDDRYWWKN UniProtKB: Maltose/maltodextrin-binding periplasmic protein, NACHT, LRR and PYD domains-containing protein 5 |
-分子 #2: Oocyte-expressed protein homolog
分子 | 名称: Oocyte-expressed protein homolog / 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: 18.479176 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MVDDAGAAES QRGKQTPAHS LEQLRRLPLP PPQIRIRPWW FPVQELRDPL VFYLEAWLAD ELFGPDRAII PEMEWTSQAL LTVDIVDSG NLVEITVFGR PRVQNRVKSM LLCLAWFHRE HRARAEKMKH LEKNLKAHAS DPHSPQDPVA LEWSHPQFEK UniProtKB: Oocyte-expressed protein homolog |
-分子 #3: Ubiquitin-like protein SMT3,Transducin-like enhancer protein 6
分子 | 名称: Ubiquitin-like protein SMT3,Transducin-like enhancer protein 6 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: 59.899367 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MWSHPQFEKG TMSDSEVNQE AKPEVKPEVK PETHINLKVS DGSSEIFFKI KKTTPLRRLM EAFAKRQGKE MDSLRFLYDG IRIQADQTP EDLDMEDNDI IEAHREQIGG LFWDKEPWFW HDTLTEQLWR IFAGVHDEKA KPRDRQQAPG LGQESKAPGS C DPGTDPCP ...文字列: MWSHPQFEKG TMSDSEVNQE AKPEVKPEVK PETHINLKVS DGSSEIFFKI KKTTPLRRLM EAFAKRQGKE MDSLRFLYDG IRIQADQTP EDLDMEDNDI IEAHREQIGG LFWDKEPWFW HDTLTEQLWR IFAGVHDEKA KPRDRQQAPG LGQESKAPGS C DPGTDPCP EDASTPRPPE ASSSPPEGSQ DRNTSWGVVQ EPPGRASRFL QSISWDPEDF EDAWKRPDAL PGQSKRLAVP CK LEKMRIL AHGELVLATA ISSFTRHVFT CGRRGIKVWS LTGQVAEDRF PESHLPIQTP GAFLRTCLLS SNSRSLLTGG YNL ASVSVW DLAAPSLHVK EQLPCAGLNC QALDANLDAN LAFASFTSGV VRIWDLRDQS VVRDLKGYPD GVKSIVVKGY NIWT GGPDA CLRCWDQRTI MKPLEYQFKS QIMSLSHSPQ EDWVLLGMAN GQQWLQSTSG SQRHMVGQKD SVILSVKFSP FGQWW ASVG MDDFLGVYSM PAGTKVFEVP EMSPVTCCDV SSNNRLVVTG SGEHASVYQI TY UniProtKB: Ubiquitin-like protein SMT3, Transducin-like enhancer protein 6 |
-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 K2 SUMMIT (4k x 4k) 平均電子線量: 51.336 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): 1.8 µm / 最小 デフォーカス(公称値): 1.1 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: NONE |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.01 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 280159 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |