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-Structure paper
タイトル | Structurally derived universal mechanism for the catalytic cycle of the tail-anchored targeting factor Get3. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 29, Issue 8, Page 820-830, Year 2022 |
掲載日 | 2022年7月18日 |
著者 | Michelle Y Fry / Vladimíra Najdrová / Ailiena O Maggiolo / Shyam M Saladi / Pavel Doležal / William M Clemons / |
PubMed 要旨 | Tail-anchored (TA) membrane proteins, accounting for roughly 2% of proteomes, are primarily targeted posttranslationally to the endoplasmic reticulum membrane by the guided entry of TA proteins (GET) ...Tail-anchored (TA) membrane proteins, accounting for roughly 2% of proteomes, are primarily targeted posttranslationally to the endoplasmic reticulum membrane by the guided entry of TA proteins (GET) pathway. For this complicated process, it remains unknown how the central targeting factor Get3 uses nucleotide to facilitate large conformational changes to recognize then bind clients while also preventing exposure of hydrophobic surfaces. Here, we identify the GET pathway in Giardia intestinalis and present the structure of the Get3-client complex in the critical postnucleotide-hydrolysis state, demonstrating that Get3 reorganizes the client-binding domain (CBD) to accommodate and shield the client transmembrane helix. Four additional structures of GiGet3, spanning the nucleotide-free (apo) open to closed transition and the ATP-bound state, reveal the details of nucleotide stabilization and occluded CBD. This work resolves key conundrums and allows for a complete model of the dramatic conformational landscape of Get3. |
リンク | Nat Struct Mol Biol / PubMed:35851188 |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.23 - 8.46 Å |
構造データ | EMDB-25373: Get3 bound to ADP and the transmembrane domain of the tail-anchored protein Bos1 - nucleotide binding domain map EMDB-25374: Get3 bound to ADP and the transmembrane domain of the tail-anchored protein Bos1 - overall map EMDB-25375: Nucleotide-free Get3 in the closed form PDB-7spy: PDB-7spz: |
化合物 | ChemComp-ATP: ChemComp-MG: ChemComp-ZN: ChemComp-SO4: ChemComp-HOH: ChemComp-ADP: |
由来 |
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キーワード | CHAPERONE / Tail-anchored membrane protein targeting Deviant Walker A ATPase targeting factor |