+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6iyc | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Recognition of the Amyloid Precursor Protein by Human gamma-secretase | |||||||||
要素 |
| |||||||||
キーワード | MEMBRANE PROTEIN / Complex | |||||||||
機能・相同性 | 機能・相同性情報 Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / positive regulation of coagulation / negative regulation of core promoter binding / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / protein catabolic process at postsynapse / positive regulation of amyloid precursor protein biosynthetic process ...Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / positive regulation of coagulation / negative regulation of core promoter binding / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / protein catabolic process at postsynapse / positive regulation of amyloid precursor protein biosynthetic process / positive regulation of endopeptidase activity / Noncanonical activation of NOTCH3 / sequestering of calcium ion / Notch receptor processing / choline transport / central nervous system myelination / synaptic vesicle targeting / membrane protein intracellular domain proteolysis / negative regulation of axonogenesis / regulation of resting membrane potential / T cell activation involved in immune response / NOTCH4 Activation and Transmission of Signal to the Nucleus / skin morphogenesis / growth factor receptor binding / regulation of synaptic vesicle cycle / dorsal/ventral neural tube patterning / neural retina development / L-glutamate import across plasma membrane / myeloid dendritic cell differentiation / Regulated proteolysis of p75NTR / cerebral cortex cell migration / regulation of phosphorylation / metanephros development / regulation of epidermal growth factor-activated receptor activity / brain morphogenesis / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / endoplasmic reticulum calcium ion homeostasis / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity / nuclear outer membrane / glutamate receptor signaling pathway / locomotion / axon midline choice point recognition / amyloid precursor protein metabolic process / smooth endoplasmic reticulum calcium ion homeostasis / regulation of canonical Wnt signaling pathway / astrocyte activation involved in immune response / aggresome / regulation of long-term synaptic potentiation / regulation of spontaneous synaptic transmission / mating behavior / embryonic limb morphogenesis / skeletal system morphogenesis / cell fate specification / NMDA selective glutamate receptor signaling pathway / ciliary rootlet / myeloid cell homeostasis / regulation of postsynapse organization / Lysosome Vesicle Biogenesis / azurophil granule membrane / PTB domain binding / G protein-coupled dopamine receptor signaling pathway / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; アスパラギン酸プロテアーゼ / Golgi-associated vesicle / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / Golgi cisterna membrane / adult behavior / positive regulation of G2/M transition of mitotic cell cycle / mitochondrial transport / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / positive regulation of dendritic spine development / positive regulation of receptor recycling / nuclear envelope lumen / COPII-coated ER to Golgi transport vesicle / suckling behavior / blood vessel development / regulation of neuron projection development / heart looping / protein glycosylation / dendrite development / amyloid precursor protein catabolic process / presynaptic active zone / modulation of excitatory postsynaptic potential / regulation of peptidyl-tyrosine phosphorylation / amyloid-beta formation / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / The NLRP3 inflammasome / negative regulation of apoptotic signaling pathway / membrane protein ectodomain proteolysis / regulation of presynapse assembly 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.6 Å | |||||||||
データ登録者 | Zhou, R. / Yang, G. / Guo, X. / Zhou, Q. / Lei, J. / Shi, Y. | |||||||||
資金援助 | 中国, 1件
| |||||||||
引用 | ジャーナル: Science / 年: 2019 タイトル: Recognition of the amyloid precursor protein by human γ-secretase. 著者: Rui Zhou / Guanghui Yang / Xuefei Guo / Qiang Zhou / Jianlin Lei / Yigong Shi / 要旨: Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase is linked to Alzheimer's disease (AD). We report an atomic structure of human γ-secretase in complex with a ...Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase is linked to Alzheimer's disease (AD). We report an atomic structure of human γ-secretase in complex with a transmembrane (TM) APP fragment at 2.6-angstrom resolution. The TM helix of APP closely interacts with five surrounding TMs of PS1 (the catalytic subunit of γ-secretase). A hybrid β sheet, which is formed by a β strand from APP and two β strands from PS1, guides γ-secretase to the scissile peptide bond of APP between its TM and β strand. Residues at the interface between PS1 and APP are heavily targeted by recurring mutations from AD patients. This structure, together with that of γ-secretase bound to Notch, reveal contrasting features of substrate binding, which may be applied toward the design of substrate-specific inhibitors. | |||||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6iyc.cif.gz | 256.3 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb6iyc.ent.gz | 206.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6iyc.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 6iyc_validation.pdf.gz | 1.4 MB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 6iyc_full_validation.pdf.gz | 1.4 MB | 表示 | |
XML形式データ | 6iyc_validation.xml.gz | 43.7 KB | 表示 | |
CIF形式データ | 6iyc_validation.cif.gz | 64.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/iy/6iyc ftp://data.pdbj.org/pub/pdb/validation_reports/iy/6iyc | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
-タンパク質 , 3種, 3分子 ABE
#1: タンパク質 | 分子量: 78483.570 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NCSTN, KIAA0253, UNQ1874/PRO4317 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q92542 |
---|---|
#2: タンパク質 | 分子量: 52688.551 Da / 分子数: 1 / Mutation: Q112C / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSEN1, AD3, PS1, PSNL1 / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: P49768, 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; アスパラギン酸プロテアーゼ |
#5: タンパク質 | 分子量: 11888.622 Da / 分子数: 1 / Fragment: C83 / Mutation: V8C / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: APP, A4, AD1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P05067 |
-Gamma-secretase subunit ... , 2種, 2分子 CD
#3: タンパク質 | 分子量: 29017.943 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: APH1A, PSF, CGI-78, UNQ579/PRO1141 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q96BI3 |
---|---|
#4: タンパク質 | 分子量: 12038.029 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PSENEN, PEN2, MDS033 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q9NZ42 |
-糖 , 3種, 12分子
#6: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #7: 多糖 | beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #8: 糖 | ChemComp-NAG / |
---|
-非ポリマー , 2種, 5分子
#9: 化合物 | #10: 化合物 | |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: human gamma-secretase / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 1.5625 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 分類: 精密化 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 502450 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
|