Molecular basis for the lack of auto-inhibition of Plasmodium falciparum importin α

• Published in: Biochemical and biophysical research communications Vol. 503; no. 3; pp. 1792 - 1797
• Main Authors: Dey, Vishakha, Patankar, Swati
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10-09-2018
• Subjects: 60 APPLIED LIFE SCIENCES; PLASMODIUM; RECEPTORS; SACCHAROMYCES CEREVISIAE
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.07.115

Importin α is nuclear transport receptor that recognises nuclear localisation sequences (NLS). The protein has two domains: armadillo (ARM) repeats containing NLS-binding sites and the importin β-binding (IBB) domain. The IBB domain mimics an NLS and can bind to the ARM repeats, preventing NLS binding. This phenomenon, called auto-inhibition, is a key regulatory feature for binding and release of NLS-containing cargo by importin α and mutants that lack auto-inhibition show impaired viability in Saccharomyces cerevisiae. The genome of the human malaria parasite, Plasmodium falciparum, contains a single gene for importin α and here we show that the native protein expressed by this gene lacks auto-inhibition, suggesting that P. falciparum parasites possess unconventional mechanisms for regulation of cargo binding and release. Mutation of a single SKR motif (conserved in Plasmodium species) to KRR in P. falciparum importin α restores auto-inhibition. This is the first report of a single-celled eukaryote that has evolved with a single importin α isoform lacking auto-inhibition.
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•P. falciparum contains a single gene for importin α which lacks auto-inhibition.•Mutation of a single motif in P. falciparum importin α restores auto-inhibition.•Auto-inhibition is not crucial for viability of the parasite, unlike in yeast.•The parasite may employ unique strategies for cargo binding and release.•Lack of auto-inhibition may confer advantages to parasites for faster growth.