The Plasmodium falciparum exportome contains non‐canonical PEXEL/HT proteins. Issue 2 (9th May 2015)

• Record Type: Journal Article
• Authors: Schulze, Jana; Kwiatkowski, Marcel; Borner, Janus; Schlüter, Hartmut; Bruchhaus, Iris; Burmester, Thorsten; Spielmann, Tobias; Pick, Christian
• Is Part Of: Molecular microbiology. Volume 97:Issue 2(2015)
• Page Start: 301
• Page End: 314
• Publication Date: 2015-05-09
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13024
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>The pathogenicity of <italic>P</italic><italic>lasmodium falciparum</italic> is partly due to parasite‐induced host cell modifications. These modifications are facilitated by exported <italic>P</italic><italic>. falciparum</italic> proteins, collectively referred to as the exportome. Export of several hundred proteins is mediated by the PEXEL/HT, a protease cleavage site. The PEXEL/HT is usually comprised of five amino acids, of which R at position 1, L at position 3 and E, D or Q at position 5 are conserved and important for export. Non‐canonical PEXEL/HTs with K or H at position 1 and/or I at position 3 are presently considered non‐functional. Here, we show that non‐canonical PEXEL/HT proteins are overrepresented in <italic>P</italic><italic>. falciparum</italic> and other <italic>P</italic><italic>lasmodium</italic> species. Furthermore, we show that non‐canonical PEXEL/HTs can be cleaved and can promote export in both a REX3 and a GBP reporter, but not in a KAHRP reporter, indicating that non‐canonical PEXEL/HTs are functional in concert with a supportive sequence environment. We then selected <italic>P</italic><italic>. falciparum</italic> proteins with a non‐canonical PEXEL/HT and show that some of these proteins are exported and that their export depends on non‐canonical PEXEL/HTs. We conclude that PEXEL/HT plasticity is higher than appreciated and that non‐canonical PEXEL/HT proteins cannot categorically be excluded from <italic>P</italic><italic>lasmodium</italic> exportome predictions.</p> </abstract>