TRG_Oom_RxLR_1

Oomycetes belong to Stramenopiles within the SAR supergroup, and they include a diverse range of eukaryotic microorganisms, including obligate parasites such as Phytophthora infestans, the world’s most economically destructive agricultural pathogen, responsible for the Irish potato blight in the 1870s, and still causing billions of euros loss yearly just in the EU. Phytophthora species are filamentous and spore-forming eukaryotic microorganisms, belonging to the class Oomycota; fungus-like organisms that are not true fungi, but are susceptible to many fungicides. It is an obligate parasite, adapted for infecting plants of the Solanaceae family, including potato, tomato, aubergine, and chili peppers (Potato late blight and tuber blight).

The conserved Arg-X-Leu-Arg (RxLR) sequence motif was shown to play an essential role in transporting the secreted pathogen proteins across the plant membrane (Dou,2008). Interestingly, the processing of the motif shows similarities to the PEXEL motif in Plasmodium falciparum. Both PEXEL and RxLR motif containing proteins have a preceding signal peptide and they get N-terminally acetylated after cleavage. However, while the PEXEL motif is partially retained in P. falciparum, the RxLR version seems to be completely cleaved in P. infestans (Wawra,2017). In AVR3a (D0NPN8) the acetylation occurs right after the RxLR motif is cleaved at Lys-48, the first amino acid downstream of the RxLR(Wawra,2017). It was proposed that fungal RxLR motif enables binding the phospholipid, phosphatidylinositol-3-phosphate (PI3P) and pathogen entry might involve lipid raft-mediated endocytosis. As PI3P is abundant at the plant cell surface, it may mediate entry of some effectors to the host cell cytoplasm (Kale,2010). This observation was challenged in general as this mechanism could not be reproduced(Wawra,2012) at least not in the case of AVR3a (D0NPN8). Considering all evidence, the RxLR motif is involved in secretion rather than working as an uptake motif; however, the exact mechanism of action is still elusive.

RxLR dEER motif containing proteins were associated with functions perturbing host cell processes: Avh241 (E0W4Y2) localizes to the plasma membrane and induces cell death (Yu,2012); PexRD2 (G3KFL3) interacts with MAPKKKε, perturbs the signaling pathway and blocks cell death (King,2014). The AIM motif of the effector protein PexRD54 (D0NBE6) binds to ATG8 and perturbs host-selective autophagy (Maqbool,2016). AVRblb2 (D0P1A8) is also an RxLR motif containing protein without a recognizable downstream dEER motif, that prevents the secretion of C14 protease to the haustorial interface (Bozkurt,2011).

Notably, RxLR-like segments with similar functions seem to be present in more distant organisms too, such as the pathogenic fungi Puccinia striiformis (Gu,2011) (KRLT) and Melampsora lini (Rafiqi,2010) (KFLK, RFYR). However, slight changes in the sequence make it hard to unambiguously correlate these motifs with the Oomycete version of the motif.

The RxLR motif is reminiscent of the metazoan golgi-based furin processing motif R.[RK]R (see entry CLV_PCSK_FUR_1).