4JJM

Structure of a cyclophilin from Citrus sinensis (CsCyp) in complex with cyclosporin A

4JJM の概要

• エントリーDOI: 10.2210/pdb4jjm/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000142
• 分子名称: Peptidyl-prolyl cis-trans isomerase, cyclosporin A (3 entities in total)
• 機能のキーワード: cyclophilin, isomerase-immunosuppressant complex, isomerase/immunosuppressant
• 由来する生物種: Citrus sinensis (Valencia orange,apfelsine,naranja,navel orange,sweet orange); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 39237.07

構造登録者

Campos, B.M.,Ambrosio, A.L.B.,Souza, T.A.C.B.,Barbosa, J.A.R.G.,Benedetti, C.E. (登録日: 2013-03-08, 公開日: 2013-06-12, 最終更新日: 2023-12-06)

主引用文献

Campos, B.M.,Sforca, M.L.,Ambrosio, A.L.,Domingues, M.N.,Brasil de Souza Tde, A.,Barbosa, J.A.R.G.,Paes Leme, A.F.,Perez, C.A.,Whittaker, S.B.,Murakami, M.T.,Zeri, A.C.,Benedetti, C.E.
A redox 2-cys mechanism regulates the catalytic activity of divergent cyclophilins.
Plant Physiol., 162:1311-1323, 2013

PubMed Abstract: The citrus (Citrus sinensis) cyclophilin CsCyp is a target of the Xanthomonas citri transcription activator-like effector PthA, required to elicit cankers on citrus. CsCyp binds the citrus thioredoxin CsTdx and the carboxyl-terminal domain of RNA polymerase II and is a divergent cyclophilin that carries the additional loop KSGKPLH, invariable cysteine (Cys) residues Cys-40 and Cys-168, and the conserved glutamate (Glu) Glu-83. Despite the suggested roles in ATP and metal binding, the functions of these unique structural elements remain unknown. Here, we show that the conserved Cys residues form a disulfide bond that inactivates the enzyme, whereas Glu-83, which belongs to the catalytic loop and is also critical for enzyme activity, is anchored to the divergent loop to maintain the active site open. In addition, we demonstrate that Cys-40 and Cys-168 are required for the interaction with CsTdx and that CsCyp binds the citrus carboxyl-terminal domain of RNA polymerase II YSPSAP repeat. Our data support a model where formation of the Cys-40-Cys-168 disulfide bond induces a conformational change that disrupts the interaction of the divergent and catalytic loops, via Glu-83, causing the active site to close. This suggests a new type of allosteric regulation in divergent cyclophilins, involving disulfide bond formation and a loop-displacement mechanism.

PubMed: 23709667
DOI: 10.1104/pp.113.218339

実験手法

X-RAY DIFFRACTION (2.09 Å)