Unravelling the structure-function features of Ani2, a dual chaperone from Schizosaccharomyces pombe.

Histone chaperones play significant roles in histone storage, transport, and assembly to form nucleosomes. Nucleoplasmin, a family of histone chaperones, has been reported from across the eukaryotic spectrum. Among these, the FK506-binding protein (FKBP) nucleoplasmin class, present in yeast, plants, and arthropods, possesses a nucleoplasmin core domain at the N-terminus, a central acidic stretch, and a characteristic C-terminal FKBP domain. CENP-A N-terminal domain isomerase 2 (Ani2) is an FKBP nucleoplasmin reported from the fission yeast, Schizosaccharomyces pombe. Ani2 has not been characterized in terms of its domain organization, chaperoning functions, and structural features. Herein, we undertook a domain-dissection approach and report the structural and in vitro functional attributes of Ani2. The N-terminal nucleoplasmin domain formed a pentamer, and the C-terminal domain (CTD) revealed a characteristic monomeric fold of an FKBP. The N-terminal domain (NTD) showed histone chaperone activity in vitro, and the FKBP domain functioned as a prolyl isomerase, confirming that this is a dual chaperone. Moreover, the CTD efficiently binds to the immunosuppressive compounds FK506 and rapamycin.