4C9J

Structure of yeast mitochondrial ADP/ATP carrier isoform 3 inhibited by carboxyatractyloside (P212121 crystal form)

4C9J の概要

• エントリーDOI: 10.2210/pdb4c9j/pdb
• 関連するPDBエントリー: 4C9G 4C9H 4C9Q
• 分子名称: ADP, ATP CARRIER PROTEIN 3, Carboxyatractyloside, CARDIOLIPIN (3 entities in total)
• 機能のキーワード: mitochondrial carrier, transport protein
• 由来する生物種: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST)
• 細胞内の位置: Mitochondrion inner membrane; Multi-pass membrane protein: P18238
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80837.85

構造登録者

Ruprecht, J.J.,Hellawell, A.M.,Harding, M.,Crichton, P.G.,McCoy, A.J.,Kunji, E.R.S. (登録日: 2013-10-02, 公開日: 2014-01-22, 最終更新日: 2023-12-20)

主引用文献

Ruprecht, J.J.,Hellawell, A.M.,Harding, M.,Crichton, P.G.,Mccoy, A.J.,Kunji, E.R.S.
Structures of Yeast Mitochondrial Adp/ATP Carriers Support a Domain-Based Alternating-Access Transport Mechanism
Proc.Natl.Acad.Sci.USA, 111:E426-, 2014

PubMed Abstract: The mitochondrial ADP/ATP carrier imports ADP from the cytosol and exports ATP from the mitochondrial matrix. The carrier cycles by an unresolved mechanism between the cytoplasmic state, in which the carrier accepts ADP from the cytoplasm, and the matrix state, in which it accepts ATP from the mitochondrial matrix. Here we present the structures of the yeast ADP/ATP carriers Aac2p and Aac3p in the cytoplasmic state. The carriers have three domains and are closed at the matrix side by three interdomain salt-bridge interactions, one of which is braced by a glutamine residue. Glutamine braces are conserved in mitochondrial carriers and contribute to an energy barrier, preventing the conversion to the matrix state unless substrate binding occurs. At the cytoplasmic side a second salt-bridge network forms during the transport cycle, as demonstrated by functional analysis of mutants with charge-reversed networks. Analyses of the domain structures and properties of the interdomain interfaces indicate that interconversion between states involves movement of the even-numbered α-helices across the surfaces of the odd-numbered α-helices by rotation of the domains. The odd-numbered α-helices have an L-shape, with proline or serine residues at the kinks, which functions as a lever-arm, coupling the substrate-induced disruption of the matrix network to the formation of the cytoplasmic network. The simultaneous movement of three domains around a central translocation pathway constitutes a unique mechanism among transport proteins. These findings provide a structural description of transport by mitochondrial carrier proteins, consistent with an alternating-access mechanism.

PubMed: 24474793
DOI: 10.1073/PNAS.1320692111

実験手法

X-RAY DIFFRACTION (3.397 Å)