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Cited by 5Nuclear Structure and FunctionToxoplasma gondii Research StudiesProtein Structure and Dynamics

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Toxoplasma Gondii Importin α Shows Weak Auto-Inhibition

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Bhambid, Manasi, Dey, Vishakha, Walunj, Sujata, Patankar, Swati·2023·The Protein Journal
DOI 10.1007/s10930-023-10128-2

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Abstract

Importin α is a nuclear transporter that binds to nuclear localization signals (NLSs), consisting of 7-20 positively charged amino acids found within cargo proteins. In addition to cargo binding, intramolecular interactions also occur within the importin α protein due to binding between the importin β-binding (IBB) domain and the NLS-binding sites, a phenomenon called auto-inhibition. The interactions causing auto-inhibition are driven by a stretch of basic residues, similar to an NLS, in the IBB domain. Consistent with this, importin α proteins that do not have some of these basic residues lack auto-inhibition; a naturally occurring example of such a protein is found in the apicomplexan parasite Plasmodium falciparum. In this report, we show that importin α from another apicomplexan parasite, Toxoplasma gondii, harbors basic residues (KKR) in the IBB domain and exhibits auto-inhibition. This protein has a long, unstructured hinge motif (between the IBB domain and the NLS-binding sites) that does not contribute to auto-inhibition. However, the IBB domain may have a higher propensity to form an α-helical structure, positioning the wild-type KKR motif in an orientation that results in weaker interactions with the NLS-binding site than a KRR mutant. We conclude that the importin α protein from T. gondii shows auto-inhibition, exhibiting a different phenotype from that of P. falciparum importin α. However, our data indicate that T. gondii importin α may have a low strength of auto-inhibition. We hypothesize that low levels of auto-inhibition may confer an advantage to these important human pathogens.

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Metadata

Authors
Bhambid, M., Dey, V., Walunj, S., & Patankar, S.
Affiliations
Indian Institute of Technology Bombay (IN)
Corresponding author
Patankar, Swati
ORCID
Venue
The Protein Journal
Publisher
Springer Science and Business Media LLC
Published
2023-06-07
Volume
42
Issue
4
Pages
327-342
ISSN
  • 1572-3887 (ISSN-L)
  • 1875-8355
DOI
10.1007/s10930-023-10128-2
OpenAlex
W4379599515
Cited by
5
References
7
Citations by year
2026: 2 · 2025: 2 · 2024: 1
FWCI
0.44
Type
journal article
Language
en
Open access
Licence
Locations
  • The Protein Journal (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Human Resource Development Group
  • Department of Biotechnology- The World Academy of Sciences
  • Indian Institute of Technology Bombay-Monash Research Academy
  • Department of Science and Technology, Science and Engineering Research Board, India (CRG/2018/000129)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
importin alpha, Toxoplasma gondii, autoinhibition, nuclear localization signal, protein conformation, nuclear transport, Apicomplexa, Plasmodium falciparum
MeSH terms
Amino Acid Sequence, Binding Sites, Humans, Protein Binding, Toxoplasma, Nuclear Localization Signals, alpha Karyopherins, beta Karyopherins

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