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-Structure paper
タイトル | Glutathione binding to the plant Atm3 transporter and implications for the conformational coupling of ABC transporters. |
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ジャーナル・号・ページ | Elife, Vol. 11, Year 2022 |
掲載日 | 2022年3月25日 |
著者 | Chengcheng Fan / Douglas C Rees / |
PubMed 要旨 | The ATP binding cassette (ABC) transporter of mitochondria (Atm) from (Atm3) has been implicated in the maturation of cytosolic iron-sulfur proteins and heavy metal detoxification, plausibly by ...The ATP binding cassette (ABC) transporter of mitochondria (Atm) from (Atm3) has been implicated in the maturation of cytosolic iron-sulfur proteins and heavy metal detoxification, plausibly by exporting glutathione derivatives. Using single-particle cryo-electron microscopy, we have determined four structures of Atm3 in three different conformational states: two inward-facing conformations (with and without bound oxidized glutathione [GSSG]), together with closed and outward-facing states stabilized by MgADP-VO. These structures not only provide a structural framework for defining the alternating access transport cycle, but also reveal the paucity of cysteine residues in the glutathione binding site that could potentially form inhibitory mixed disulfides with GSSG. Despite extensive efforts, we were unable to prepare the ternary complex of Atm3 containing both GSSG and MgATP. A survey of structurally characterized type IV ABC transporters that includes Atm3 establishes that while nucleotides are found associated with all conformational states, they are effectively required to stabilize occluded, closed, and outward-facing conformations. In contrast, transport substrates have only been observed associated with inward-facing conformations. The absence of structures with dimerized nucleotide binding domains containing both nucleotide and transport substrate suggests that this form of the ternary complex exists only transiently during the transport cycle. |
リンク | Elife / PubMed:35333177 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 - 3.95 Å |
構造データ | EMDB-24182, PDB-7n58: EMDB-24183, PDB-7n59: EMDB-24184, PDB-7n5a: EMDB-24185, PDB-7n5b: |
化合物 | ChemComp-GDS: ChemComp-ADP: ChemComp-VO4: ChemComp-MG: |
由来 |
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キーワード | MEMBRANE PROTEIN / ABC transporter / ATPase |