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基本情報
登録情報 | データベース: EMDB / ID: EMD-22152 | |||||||||
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タイトル | CryoEM structure of GIRK2-PIP2*** - G protein-gated inwardly rectifying potassium channel GIRK2 with PIP2 | |||||||||
![]() | CryoEM structure of GIRK2-PIP2*** - G protein-gated inwardly rectifying potassium channel GIRK2 with PIP2 | |||||||||
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機能・相同性 | ![]() G-protein activated inward rectifier potassium channel activity / regulation of monoatomic ion transmembrane transport / monoatomic ion channel complex / potassium ion import across plasma membrane / ![]() 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | ![]() ![]() | |||||||||
![]() | Mathiharan YK / Glaaser IW / Skiniotis G / Slesinger PA | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into GIRK2 channel modulation by cholesterol and PIP. 著者: Yamuna Kalyani Mathiharan / Ian W Glaaser / Yulin Zhao / Michael J Robertson / Georgios Skiniotis / Paul A Slesinger / ![]() 要旨: G-protein-gated inwardly rectifying potassium (GIRK) channels are important for determining neuronal excitability. In addition to G proteins, GIRK channels are potentiated by membrane cholesterol, ...G-protein-gated inwardly rectifying potassium (GIRK) channels are important for determining neuronal excitability. In addition to G proteins, GIRK channels are potentiated by membrane cholesterol, which is elevated in the brains of people with neurodegenerative diseases such as Alzheimer's dementia and Parkinson's disease. The structural mechanism of cholesterol modulation of GIRK channels is not well understood. In this study, we present cryo- electron microscopy (cryoEM) structures of GIRK2 in the presence and absence of the cholesterol analog cholesteryl hemisuccinate (CHS) and phosphatidylinositol 4,5-bisphosphate (PIP). The structures reveal that CHS binds near PIP in lipid-facing hydrophobic pockets of the transmembrane domain. Our structural analysis suggests that CHS stabilizes PIP interaction with the channel and promotes engagement of the cytoplasmic domain onto the transmembrane region. Mutagenesis of one of the CHS binding pockets eliminates cholesterol-dependent potentiation of GIRK2. Elucidating the structural mechanisms underlying cholesterol modulation of GIRK2 channels could facilitate the development of therapeutics for treating neurological diseases. VIDEO ABSTRACT. | |||||||||
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マップデータ | ![]() | 61 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 13.7 KB 13.7 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.5 KB | 表示 | ![]() |
画像 | ![]() | 89.4 KB | ||
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | CryoEM structure of GIRK2-PIP2*** - G protein-gated inwardly rectifying potassium channel GIRK2 with PIP2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.85 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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試料の構成要素
-全体 : G protein-gated inwardly rectifying potassium channel (GIRK2)
全体 | 名称: G protein-gated inwardly rectifying potassium channel (GIRK2) |
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要素 |
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-超分子 #1: G protein-gated inwardly rectifying potassium channel (GIRK2)
超分子 | 名称: G protein-gated inwardly rectifying potassium channel (GIRK2) タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: The cryoEM structure obtained in the presence of modulator PIP2. |
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由来(天然) | 生物種: ![]() ![]() ![]() |
組換発現 | 生物種: ![]() ![]() |
-分子 #1: G protein-gated inwardly rectifying potassium channel GIRK2
分子 | 名称: G protein-gated inwardly rectifying potassium channel GIRK2 タイプ: protein_or_peptide / ID: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() ![]() |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MAKRKIQRYV RKDGKCNVH H GNVRETYR YL TDIFTTL VDL KWRFNL LIFV MVYTV TWLFF GMIW WLIAYI RGD MDHIEDP SW TPCVTNLN G FVSAFLFSI ETETTIGYGY RVITDKCPE G IILLLIQS VL GSIVNAF MVG CMFVKI SQPK KRAET ...文字列: MAKRKIQRYV RKDGKCNVH H GNVRETYR YL TDIFTTL VDL KWRFNL LIFV MVYTV TWLFF GMIW WLIAYI RGD MDHIEDP SW TPCVTNLN G FVSAFLFSI ETETTIGYGY RVITDKCPE G IILLLIQS VL GSIVNAF MVG CMFVKI SQPK KRAET LVFST HAVI SMRDGK LCL MFRVGDL RN SHIVEASI R AKLIKSKQT SEGEFIPLNQ TDINVGYYT G DDRLFLVS PL IISHEIN QQS PFWEIS KAQL PKEEL EIVVI LEGM VEATGM TCQ ARSSYIT SE ILWGYRFT P VLTLEDGFY EVDYNSFHET YETSTPSLS A KELAELAN RA ESNSLEV LFQ |
-実験情報
-構造解析
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試料の集合状態 | particle |
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試料調製
濃度 | 7 mg/mL | |||||||||||||||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 200 / 前処理 - タイプ: GLOW DISCHARGE | |||||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 293 K / 装置: FEI VITROBOT MARK IV | |||||||||||||||||||||
詳細 | GIRK2 with modulator PIP2 |
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電子顕微鏡法
顕微鏡 | TFS KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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 |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 6480 / 平均露光時間: 3.0 sec. / 平均電子線量: 83.0 e/Å2 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |