Cecilia P. Sanchez, Pintu Patra, Shih-Ying Scott Chang, Christos Karathanasis, Lukas Hanebutte, Nicole Kilian, Marek Cyrklaff, Mike Heilemann, Ulrich S. Schwarz, Mikhail Kudryashev, Michael Lanzer
- 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.
MetadatenAuthor: | Cecilia P. Sanchez, Pintu Patra, Shih-Ying Scott Chang, Christos KarathanasisORCiDGND, Lukas Hanebutte, Nicole Kilian, Marek Cyrklaff, Mike HeilemannORCiDGND, Ulrich S. Schwarz, Mikhail KudryashevORCiDGND, Michael Lanzer |
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URN: | urn:nbn:de:hebis:30:3-627647 |
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DOI: | https://doi.org/10.1111/mmi.14811 |
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ISSN: | 1365-2958 |
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Parent Title (English): | Molecular microbiology |
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Publisher: | Wiley-Blackwell |
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Place of publication: | Oxford [u.a.] |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/09/13 |
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Date of first Publication: | 2021/09/13 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2022/05/02 |
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Tag: | actin; ankyrin; erythrocyte; malaria; microscopy; virulence factor |
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Volume: | 117 |
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Issue: | 2 |
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Page Number: | 19 |
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First Page: | 274 |
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Last Page: | 292 |
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Note: | 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. |
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HeBIS-PPN: | 494893877 |
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Institutes: | Biochemie, Chemie und Pharmazie |
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Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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