Kelch13 location and interactome. (A) Fluorescence microscopy images showing parasites with endogenously GFP-tagged Kelch13 (K13) with coexpressed STVR-SDEL (ER), Sec13p (ER exit sites), P40 (phosphatidylinositol 3-phosphate sensor: food vacuole), ACP (apicoplast), or endogenously GFP-tagged mutated Kelch13 (K13C580Y) with episomal mCherry-Kelch13wt. (Bottom) Most common arrangement of markers in single-nucleus trophozoites. (B) Scheme of DiQ-BioID. (C) Rapalog-dependent recruitment of the biotinylizer (BirA*-FRB) to endogenously GFP- and FKBP-tagged Kelch13 (FKBPK13). (E) Fluorescence microscopy of parasites with endogenously 2xFKBP-GFP-2xFKBP–tagged Eps15 episomally expressing mCherry-Kelch13. Although Kelch13 foci rarely overlapped with secretory pathway markers [endoplasmic
reticulum (ER) and Golgi], they were frequently in the vicinity of parts of the ER that were near the FV. Kelch13 foci were also found close to the apicoplast, which itself is located
in proximity of the FV. Notably, the resistance conferring
form of Kelch13 (Kelch13C580Y; Cys580→Tyr) fully colocalized with episomally expressed wild-type Kelch13 (wtKelch13).
Birnbaum J, Scharf S, Schmidt S, Jonscher E, Hoeijmakers WAM, Flemming S, Toenhake CG, Schmitt M, Sabitzki R, Bergmann B, Fröhlke U, Mesén-Ramírez P, Blancke Soares A, Herrmann H, Bártfai R, Spielmann T. A Kelch13-defined endocytosis pathway mediates artemisinin resistance in malaria parasites. Science. 2020 Jan 3;367(6473):51-59.
Other associated proteins
PFID | Formal Annotation |
---|---|
PF3D7_0208500 | acyl carrier protein |
PF3D7_1017300 | golgi re-assembly stacking protein 2 |
PF3D7_1230700 | protein transport protein SEC13 |
PF3D7_1343700 | kelch protein K13 |
STEVOR | STEVOR |