TY  - JOUR
A1  - Hempelmann, Alexander
A1  - Hartleb, Laura
A1  - van Straaten, Monique
A1  - Hashemi, Hamidreza
A1  - Zeelen, Johan P.
A1  - Bongers, Kevin
A1  - Papavasiliou, F. Nina
A1  - Engstler, Markus
A1  - Stebbins, C. Erec
A1  - Jones, Nicola G.
T1  - Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome
JF  - Cell Reports
N2  - The dense variant surface glycoprotein (VSG) coat of African trypanosomes represents the primary host-pathogen interface. Antigenic variation prevents clearing of the pathogen by employing a large repertoire of antigenically distinct VSG genes, thus neutralizing the host’s antibody response. To explore the epitope space of VSGs, we generate anti-VSG nanobodies and combine high-resolution structural analysis of VSG-nanobody complexes with binding assays on living cells, revealing that these camelid antibodies bind deeply inside the coat. One nanobody causes rapid loss of cellular motility, possibly due to blockage of VSG mobility on the coat, whose rapid endocytosis and exocytosis are mechanistically linked to Trypanosoma brucei propulsion and whose density is required for survival. Electron microscopy studies demonstrate that this loss of motility is accompanied by rapid formation and shedding of nanovesicles and nanotubes, suggesting that increased protein crowding on the dense membrane can be a driving force for membrane fission in living cells.
KW  - African trypanosome
KW  - host-pathogen interaction
KW  - variant surface glycoproteins
KW  - immune epitope mapping
KW  - structural biology
KW  - nanovesicle formation
KW  - nanotube formation
KW  - protein crowding
KW  - membrane fission
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270285
VL  - 37
IS  - 5
ER  -