TY  - JOUR
A1  - Sanchez, Cecilia P.
A1  - Patra, Pintu
A1  - Scott Chang, Shih-Ying
A1  - Karathanasis, Christos
A1  - Hanebutte, Lukas
A1  - Kilian, Nicole
A1  - Cyrklaff, Marek
A1  - Heilemann, Mike
A1  - Schwarz, Ulrich S.
A1  - Kudryashev, Mikhail
A1  - Lanzer, Michael
T1  - KAHRP dynamically relocalizes to remodeled actin junctions and associates with knob spirals in Plasmodium falciparum-infected erythrocytes
T2  - Molecular microbiology
N2  - The knob-associated histidine-rich protein (KAHRP) plays a pivotal role in the pathophysiology of Plasmodium falciparum malaria by forming membrane protrusions in infected erythrocytes, which anchor parasite-encoded adhesins to the membrane skeleton. The resulting sequestration of parasitized erythrocytes in the microvasculature leads to severe disease. Despite KAHRP being an important virulence factor, its physical location within the membrane skeleton is still debated, as is its function in knob formation. Here, we show by super-resolution microscopy that KAHRP initially associates with various skeletal components, including ankyrin bridges, but eventually colocalizes with remnant actin junctions. We further present a 35 Å map of the spiral scaffold underlying knobs and show that a KAHRP-targeting nanoprobe binds close to the spiral scaffold. Single-molecule localization microscopy detected ~60 KAHRP molecules/knob. We propose a dynamic model of KAHRP organization and a function of KAHRP in attaching other factors to the spiral scaffold.
KW  - actin
KW  - ankyrin
KW  - erythrocyte
KW  - malaria
KW  - microscopy
KW  - virulence factor
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/64553
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-645539
SN  - 1365-2958
N1  - This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Projektnummer 240245660—SFB 1129 (ML and USS) and SFB 807 (CK and MH). MK and S-YC are funded by the Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation. MK is funded by the Heisenberg Program from the DFG (KU 3222/3-1). Open Access funding enabled and organized by Projekt DEAL.
N1  - Early View: Online Version before inclusion in an issue.
N1  - Version of Record: http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:hebis:30:3-627647
VL  - 2021
IS  - online version before inclusion in an issue
SP  - 1
EP  - 19
PB  - Wiley-Blackwell
CY  - Oxford [u.a.]
ER  -