PDB-8jqh: Cryo EM map of full length PLC gamma 2 in autoinhibition state

基本情報

• 登録情報: データベース: PDB / ID: 8jqh
• タイトル: Cryo EM map of full length PLC gamma 2 in autoinhibition state
• 要素: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2
• キーワード: HYDROLASE / PLCg2 / PLC gamma 2

機能・相同性

分子機能:

inositol trisphosphate biosynthetic process / regulation of calcineurin-NFAT signaling cascade / positive regulation of dendritic cell cytokine production / follicular B cell differentiation / phosphoinositide phospholipase C / antifungal innate immune response / positive regulation of interleukin-23 production / cellular response to lectin / response to yeast / phosphorylation-dependent protein binding / positive regulation of cell cycle G1/S phase transition / phosphatidylinositol metabolic process / Toll Like Receptor 4 (TLR4) Cascade / positive regulation of phagocytosis, engulfment / cell activation / positive regulation of neuroinflammatory response / Erythropoietin activates Phospholipase C gamma (PLCG) / phospholipase C activity / phosphatidylinositol-4,5-bisphosphate phospholipase C activity / phosphatidylinositol biosynthetic process / programmed cell death / macrophage activation involved in immune response / phospholipid catabolic process / cellular response to lipid / regulation of canonical NF-kappaB signal transduction / negative regulation of programmed cell death / positive regulation of macrophage cytokine production / toll-like receptor signaling pathway / phosphatidylinositol-mediated signaling / Dectin-2 family / positive regulation of NLRP3 inflammasome complex assembly / Synthesis of IP3 and IP4 in the cytosol / intracellular vesicle / positive regulation of reactive oxygen species biosynthetic process / stimulatory C-type lectin receptor signaling pathway / Fc-epsilon receptor signaling pathway / B cell activation / positive regulation of intracellular signal transduction / regulation of lipid metabolic process / positive regulation of interleukin-10 production / positive regulation of receptor internalization / Generation of second messenger molecules / positive regulation of epithelial cell migration / positive regulation of type I interferon production / Role of phospholipids in phagocytosis / response to axon injury / GPVI-mediated activation cascade / release of sequestered calcium ion into cytosol / phosphotyrosine residue binding / positive regulation of interleukin-12 production / FCERI mediated Ca+2 mobilization / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / B cell differentiation / FCGR3A-mediated IL10 synthesis / cellular response to calcium ion / protein tyrosine kinase binding / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / lipopolysaccharide-mediated signaling pathway / B cell receptor signaling pathway / FCERI mediated MAPK activation / calcium-mediated signaling / platelet activation / positive regulation of interleukin-6 production / CLEC7A (Dectin-1) signaling / ruffle membrane / Wnt signaling pathway / Signaling by CSF1 (M-CSF) in myeloid cells / positive regulation of tumor necrosis factor production / DAP12 signaling / T cell receptor signaling pathway / scaffold protein binding / Potential therapeutics for SARS / positive regulation of canonical NF-kappaB signal transduction / positive regulation of MAPK cascade / intracellular signal transduction / membrane raft / positive regulation of gene expression / protein kinase binding / perinuclear region of cytoplasm / extracellular exosome / plasma membrane / cytosol / cytoplasm

ドメイン・相同性:

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, SH3 domain / : / Phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma / PLC-gamma, C-terminal SH2 domain / PLC-gamma, N-terminal SH2 domain / PLCG EF-hand motif 2 / Pleckstrin homology domain / Phosphoinositide phospholipase C family / Phospholipase C, phosphatidylinositol-specific, Y domain / Phosphatidylinositol-specific phospholipase C, Y domain / Phosphatidylinositol-specific phospholipase Y-box domain profile. / Phospholipase C, catalytic domain (part); domain Y / Phosphatidylinositol-specific phospholipase C, X domain / Phosphatidylinositol-specific phospholipase C, X domain / Phospholipase C, catalytic domain (part); domain X / Phosphatidylinositol-specific phospholipase X-box domain profile. / PLC-like phosphodiesterase, TIM beta/alpha-barrel domain superfamily / Protein kinase C conserved region 2 (CalB) / C2 domain / C2 domain / C2 domain profile. / C2 domain superfamily / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / EF-hand domain pair / PH-like domain superfamily

構成要素:

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

• 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: 4.2 Å
• データ登録者: Shin, Y.-C. / Liao, M.

資金援助

1件

組織	認可番号	国
Not funded

引用

ジャーナル: Sci Adv / 年: 2024
タイトル: The crystal and cryo-EM structures of PLCγ2 reveal dynamic interdomain recognitions in autoinhibition.
著者: Young-Cheul Shin / Ashlee Marie Plummer-Medeiros / Alison Mungenast / Hyeong-Wook Choi / Karen TenDyke / Xiaojie Zhu / Jennifer Shepard / Kristen Sanders / Ningning Zhuang / Liang Hu / Dongming Qian / Kangkang Song / Chen Xu / John Wang / Suresh B Poda / Maofu Liao / Yu Chen /
要旨: Phospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multidomain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCγ2 activity modulation. Here we determined three structures of human PLCγ2 in autoinhibited states, which reveal dynamic interactions at the autoinhibition interface, involving the conformational flexibility of the Src homology 3 (SH3) domain in the inhibitory region, and its previously unknown interaction with a carboxyl-terminal helical domain in the core region. We also determined a structure of PLCγ2 bound to the kinase domain of fibroblast growth factor receptor 1 (FGFR1), which demonstrates the recognition of FGFR1 by the nSH2 domain in the inhibitory region of PLCγ2. Our results provide structural insights into PLCγ2 regulation that will facilitate future mechanistic studies to understand the entire activation process.

#1: ジャーナル: Biorxiv / 年: 2023
タイトル: The crystal and cryo-EM structures of PLC gamma 2 reveal dynamic inter-domain recognitions in autoinhibition
著者: Shin, Y.C. / Plummer-Medeiros, A.M. / Mungenast, A. / Choi, H.W. / TenDyke, K. / Zhu, X. / Shepard, J. / Zhuang, N. / Hu, L. / Qian, D. / Song, K. / Xu, C. / Wang, J. / Poda, S.B. / Liao, M. / Chen, Y.

履歴

登録	2023年6月14日	登録サイト: PDBJ / 処理サイト: PDBC
改定 1.0	2024年12月11日	Provider: repository / タイプ: Initial release

集合体

登録構造単位

A: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

概要:

• 148 kDa, 1 ポリマー

構成要素の詳細:

	分子量 (理論値)	分子数
合計 (水以外)	148,075	1
ポリマ－	148,075	1
非ポリマー	0	0
水	0	0

1

概要:

• 登録構造と同一
• 登録者が定義した集合体
• 根拠: 電子顕微鏡法, not applicable

対称操作:

タイプ	名称	対称操作	数
identity operation	1_555		1

要素

#1: タンパク質

A 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 / Phosphoinositide phospholipase C-gamma-2 / Phospholipase C-IV / PLC-IV / Phospholipase C-gamma-2 / PLC-gamma-2

詳細:

分子量: 148074.578 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: PLCG2 / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P16885, phosphoinositide phospholipase C

• Has protein modification: N

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: PLCg2 and FGFR1 / タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES
• 分子量: 値: 0.1478 MDa / 実験値: NO
• 由来(天然): 生物種: Homo sapiens (ヒト)
• 由来(組換発現): 生物種: Homo sapiens (ヒト) / 株: HEK293F
• 緩衝液: pH: 7.9 / 詳細: 25 mM Tris pH 7.9, 150 mM NaCl, 1mM TCEP
• 試料: 濃度: 2.7 mg/ml / 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: Talos Arctica / 画像提供: FEI Company
• 顕微鏡: モデル: FEI TALOS ARCTICA
• 電子銃: 電子線源: FIELD EMISSION GUN / 加速電圧: 200 kV / 照射モード: OTHER
• 電子レンズ: モード: OTHER / 最大 デフォーカス（公称値）: 2200 nm / 最小 デフォーカス（公称値）: 1000 nm
• 撮影: 電子線照射量: 53.0932 e/Ų / フィルム・検出器のモデル: GATAN K3 (6k x 4k)

解析

• CTF補正: タイプ: NONE
• 3次元再構成: 解像度: 4.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 24761 / 対称性のタイプ: POINT