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    Expansion of Lysine-rich repeats in Plasmodium proteins generates novel localisation sequences that target the periphery of the host Erythrocyte

    Osborne, Andrew and Thalassinos, Konstantinos and Davies, Heledd (2016) Expansion of Lysine-rich repeats in Plasmodium proteins generates novel localisation sequences that target the periphery of the host Erythrocyte. Journal of Biological Chemistry 291 , pp. 26188-26207. ISSN 0021-9258.

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    Repetitive low-complexity sequences, mostly assumed to have no function, are common in proteins that are exported by the malaria parasite into its host erythrocyte. We identify a group of exported proteins containing short lysine-rich tandemly repeated sequences that are sufficient to localise to the erythrocyte periphery where key virulence-related modifications to the plasma membrane and the underlying cytoskeleton are known to occur. Efficiency of targeting is dependent on repeat number, indicating that novel targeting modules could evolve by expansion of short lysine-rich sequences. Indeed, expression GARP fragments from different species shows that two novel targeting sequences have arisen via the process of repeat expansion in this protein. In the protein Hyp12, the targeting function of a lysine-rich sequence is masked by a neighbouring repetitive acidic sequence, further highlighting the importance of repetitive low complexity sequences. We show that sequences capable of targeting the erythrocyte periphery are present in at least nine proteins from Plasmodium falciparum, and one from Plasmodium knowlesi. We find these sequences in proteins known to be involved in erythrocyte rigidification and cytoadhesion, as well as in previously uncharacterised exported proteins. Together, these data suggest that expansion and contraction of lysine-rich repeats could generate targeting sequences de novo as well as modulate protein targeting efficiency and function in response to selective pressure.


    Item Type: Article
    Keyword(s) / Subject(s): Malaria, host-pathogen interaction, protein targeting, intrinsically disordered protein, protein evolution, cytoskeleton, Plasmodium, intracellular trafficking, tandem repeats, low complexity sequences
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Andrew Osborne
    Date Deposited: 13 Dec 2016 16:15
    Last Modified: 02 Aug 2023 17:29


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