Davies, HM;
Thalassinos, K;
Osborne, AR;
(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
(50)
pp. 26188-26207.
10.1074/jbc.M116.761213.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Expansion of Lysine-rich Repeats in Plasmodium Proteins Generates Novel Localisation Sequences that Target the Periphery of the Host Erythrocyte. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1074/jbc.M116.761213 |
| Publisher version: | http://dx.doi.org/10.1074/jbc.M116.761213 |
| Language: | English |
| Additional information: | Final version free via Creative Commons CC-BY license. |
| Keywords: | Malaria, host-pathogen interaction, protein targeting, intrinsically disordered protein, protein evolution, cytoskeleton, Plasmodium, intracellular trafficking, tandem repeats, low complexity sequences. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1527119 |
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