Novel motif in calcineurin catalytic subunit is required for septal localization of calcineurin in Aspergillus fumigatus.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Juvvadi, PR; Pemble, CW; Ma, Y; Steinbach, WJ

Published Date

  • February 2016

Published In

Volume / Issue

  • 590 / 4

Start / End Page

  • 501 - 508

PubMed ID

  • 26864964

Pubmed Central ID

  • 26864964

Electronic International Standard Serial Number (EISSN)

  • 1873-3468

Digital Object Identifier (DOI)

  • 10.1002/1873-3468.12075

Language

  • eng

Conference Location

  • England