National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
NS092695
米国
引用
ジャーナル: Cell Rep / 年: 2020 タイトル: Structures of Gα Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms. 著者: Alpay Burak Seven / Daniel Hilger / Makaía M Papasergi-Scott / Li Zhang / Qianhui Qu / Brian K Kobilka / Gregory G Tall / Georgios Skiniotis / 要旨: Many chaperones promote nascent polypeptide folding followed by substrate release through ATP-dependent conformational changes. Here we show cryoEM structures of Gα subunit folding intermediates in ...Many chaperones promote nascent polypeptide folding followed by substrate release through ATP-dependent conformational changes. Here we show cryoEM structures of Gα subunit folding intermediates in complex with full-length Ric-8A, a unique chaperone-client system in which substrate release is facilitated by guanine nucleotide binding to the client G protein. The structures of Ric-8A-Gα and Ric-8A-Gα complexes reveal that the chaperone employs its extended C-terminal region to cradle the Ras-like domain of Gα, positioning the Ras core in contact with the Ric-8A core while engaging its switch2 nucleotide binding region. The C-terminal α5 helix of Gα is held away from the Ras-like domain through Ric-8A core domain interactions, which critically depend on recognition of the Gα C terminus by the chaperone. The structures, complemented with biochemical and cellular chaperoning data, support a folding quality control mechanism that ensures proper formation of the C-terminal α5 helix before allowing GTP-gated release of Gα from Ric-8A.
Guaninenucleotide-bindingproteinG(q) subunitalpha / Guanine nucleotide-binding protein alpha-q
分子量: 42197.027 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: GNAQ, GAQ / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P50148
研究の焦点であるリガンドがあるか
N
配列の詳細
The full sequence of Ric-8A is QGEFMEPRAVADALETGEEDAVTEALRSFNREHSQSFTFDDAQQEDRKRLAKLLVSVLE ...The full sequence of Ric-8A is QGEFMEPRAVADALETGEEDAVTEALRSFNREHSQSFTFDDAQQEDRKRLAKLLVSVLE QGLSPKHRVTWLQTIRILSRDRSCLDSFASRQSLHALACYADIAISEEPIPQPPDMDVL LESLKCLCNLVLSSPTAQMLAAEARLVVRLAERVGLYRKRSYPHEVQFFDLRLLFLLTA LRTDVRQQLFQELHGVRLLTDALELTLGVAPKENPLVILPAQETERAMEILKVLFNITF DSVKREVDEEDAALYRYLGTLLRHCVMADAAGDRTEEFHGHTVNLLGNLPLKCLDVLLA LELHEGSLEFMGVNMDVINALLAFLEKRLHQTHRLKECVAPVLSVLTECARMHRPARKF LKAQVLPPLRDVRTRPEVGDLLRNKLVRLMTHLDTDVKRVAAEFLFVLCSESVPRFIKY TGYGNAAGLLAARGLMAGGRPEGQY(SEP)EDED(TPO)DTEEYREAKASINPVTGRVE EKPPNPMEGMTEEQKEHEAMKLVNMFDKLSRHRLIQPMGMSPRGHLTSLQDAMCETMEG QLSSDPDSDPD
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実験情報
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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
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試料調製
構成要素
名称: Complex of Ric-8A with G alpha q / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT