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Novel motif in calcineurin catalytic subunit is required for septal localization of calcineurin in Aspergillus fumigatus
Author(s) -
Juvvadi Praveen R.,
Pemble Charles W.,
Ma Yan,
Steinbach William J.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12075
Subject(s) - calcineurin , aspergillus fumigatus , protein subunit , chemistry , motif (music) , biochemistry , microbiology and biotechnology , biology , medicine , gene , philosophy , transplantation , aesthetics
Calcineurin heterodimer, comprised of the catalytic (CnaA) and regulatory (CnaB) subunits, localizes at the hyphal tips and septa to direct growth, septation, and disease in the human pathogen Aspergillus fumigatus . Here we discovered a novel motif (FMDVF) required for this critical CnaA septal localization, including residues Phe368, Asp370 and Phe372 overlapping the cyclosporine A‐cyclophilin A‐binding domain, CnaB‐binding helix and the FK506‐FKBP12‐binding pocket. Mutations in adjacent residues Asn367, Trp374, and Ser375 confer FK506 resistance without impacting CnaA septal localization. Modeling A. fumigatus CnaA confirmed that the FMDVF motif forms a bridge between the two known substrate‐binding motifs, PxIxIT and LxVP, and concurrent mutations (F368A D370A; F368A F372A) in the FMDVF motif disrupt CnaA‐substrate interaction at the septum.