4JJM

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

Summary for 4JJM

• Entry DOI: 10.2210/pdb4jjm/pdb
• Related PRD ID: PRD_000142
• Descriptor: Peptidyl-prolyl cis-trans isomerase, cyclosporin A (3 entities in total)
• Functional Keywords: cyclophilin, isomerase-immunosuppressant complex, isomerase/immunosuppressant
• Biological source: Citrus sinensis (Valencia orange,apfelsine,naranja,navel orange,sweet orange); More
• Total number of polymer chains: 4
• Total formula weight: 39237.07

Authors

Campos, B.M.,Ambrosio, A.L.B.,Souza, T.A.C.B.,Barbosa, J.A.R.G.,Benedetti, C.E. (deposition date: 2013-03-08, release date: 2013-06-12, Last modification date: 2023-12-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.09 Å)