TY - JOUR
T1 - The structure of the actin filament uncapping complex mediated by twinfilin
AU - Mwangangi, Dennis M.
AU - Manser, Edward
AU - Robinson, Robert C.
N1 - Funding Information:
This work was supported by Biomedical Research Council of A?STAR under the Singapore International Graduate Award (SINGA) scholarship and NMRC OFIRG/0027/2016, and by Human Frontiers Science Program award RGP0028/2018.
Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved.
PY - 2021/1/27
Y1 - 2021/1/27
N2 - Uncapping of actin filaments is essential for driving polymerization and depolymerization dynamics from capping protein-associated filaments; however, the mechanisms of uncapping leading to rapid disassembly are unknown. Here, we elucidated the x-ray crystal structure of the actin/twinfilin/capping protein complex to address the mechanisms of twinfilin uncapping of actin filaments. The twinfilin/capping protein complex binds to two G-actin subunits in an orientation that resembles the actin filament barbed end. This suggests an unanticipated mechanism by which twinfilin disrupts the stable capping of actin filaments by inducing a G-actin conformation in the two terminal actin subunits. Furthermore, twinfilin disorders critical actin-capping protein interactions, which will assist in the dissociation of capping protein, and may promote filament uncapping through a second mechanism involving V-1 competition for an actin-binding surface on capping protein. The extensive interactions with capping protein indicate that the evolutionary conserved role of twinfilin is to uncap actin filaments.
AB - Uncapping of actin filaments is essential for driving polymerization and depolymerization dynamics from capping protein-associated filaments; however, the mechanisms of uncapping leading to rapid disassembly are unknown. Here, we elucidated the x-ray crystal structure of the actin/twinfilin/capping protein complex to address the mechanisms of twinfilin uncapping of actin filaments. The twinfilin/capping protein complex binds to two G-actin subunits in an orientation that resembles the actin filament barbed end. This suggests an unanticipated mechanism by which twinfilin disrupts the stable capping of actin filaments by inducing a G-actin conformation in the two terminal actin subunits. Furthermore, twinfilin disorders critical actin-capping protein interactions, which will assist in the dissociation of capping protein, and may promote filament uncapping through a second mechanism involving V-1 competition for an actin-binding surface on capping protein. The extensive interactions with capping protein indicate that the evolutionary conserved role of twinfilin is to uncap actin filaments.
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U2 - 10.1126/sciadv.abd5271
DO - 10.1126/sciadv.abd5271
M3 - Article
C2 - 33571120
AN - SCOPUS:85099905106
VL - 7
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 5
M1 - eabd5271
ER -