Crystal Structure of Arabidopsis Cyclophilin38 Reveals a Previously Uncharacterized Immunophilin Fold and a Possible Autoinhibitory Mechanism

Abstract

Cyclophilin38 (CYP38) is one of the highly divergent cyclophilins from Arabidopsis thaliana. Here, we report the crystal structure of the At-CYP38 protein (residues 83 to 437 of 437 amino acids) at 2.39-Å resolution. The structure reveals two distinct domains: an N-terminal helical bundle and a C-terminal cyclophilin b-barrel, connected by an acidic loop. Two N-terminal b-strands become part of the C-terminal cyclophilin b-barrel, thereby making a previously undiscovered domain organization. This study shows that CYP38 does not possess peptidyl-prolyl cis/trans isomerase activity and identifies a possible interaction of CYP38 with the E-loop of chlorophyll protein47 (CP47), a component of photosystem II. The interaction of CYP38 with the E-loop of CP47 is mediated through its cyclophilin domain. The N-terminal helical domain is closely packed together with the putative C-terminal cyclophilin domain and establishes a strong intramolecular interaction, thereby preventing the access of the cyclophilin domain to other proteins. This was further verified by protein-protein interaction assays using the yeast two-hybrid system. Furthermore, the non-Leucine zipper N-terminal helical bundle contains several new elements for protein-protein interaction that may be of functional significance. Together, this study provides the structure of a plant cyclophilin and explains a possible mechanism for autoinhibition of its function through an intramolecular interaction.

Regulatory factors for the assembly of thylakoid membrane protein complexes

“…Crystal structural analysis of CYP38 revealed the presence of N-terminal helical bundle and C-terminal cyclophilin b-sheet domains. This study also uncovered a unique and previously uncharacterized domain, which may provide further understanding of the auto-inhibition mechanism of CYP38 function [36]. There are more than 50 gene models in Chlamydomonas with similarity to immunophilin proteins [75].…”

Genome wide analysis ofCyclophilingene family from rice and Arabidopsis and its comparison with yeast

“…16 CYP38 from Arabidopsis does not exhibit the PPIase activity, however it has been shown to interact with other proteins. 17 The structural analysis of cyclophilin 40 (CyP40) from mammal has revealed that the tetratricopeptide (TPR) protein domain interacts with HSP-90, indicating the crucial role played by these proteins in signaling. 18 Although cyclophilins are ubiquitous proteins, the current study has been restricted to the study of Cyclophilin gene family from two model plant species Rice and Arabidopsis and the model eukaryotic system Yeast.…”

Plant Immunophilins: A Protein Family with Diverse Functions Beyond Protein Folding Activity

“…The chloroplast thylakoid lumenal protein AtCYP38 was regarded to contain a leucine-zipper domain at N-terminus of its mature form (He et al 2004 ;Sirpiö et al 2008 ), but X-ray analysis of crystal structure revealed that the N-terminus of AtCYP38 contains a PsbQ-like domain, rather than a leucinezipper domain (Vasudevan et al 2012 ). AtCYP40 contains an N-terminus PPIase domain, a nuclear targeting signal in the middle and three TPR domains at the C-terminus.…”