Research Project
Grant-in-Aid for Challenging Exploratory Research
Amyloid fibrils of TDP-43 accumulate in patients of neurodegenerative diseases caused by mutations in the AAA chaperone VCP. Specific interaction of VCP with TDP-43 amyloid fibrils was demonstrated biochemically and by high-speed atomic force microscopy. Disease-related mutations reduced interaction between VCP and TDP-43 amyloid fibrils. VCP showed a significant disaggregation activity of TDP-43 amyloid fibrils in the presence of ATP. High-speed AFM analysis revealed that the N-D1 ring of CDC-48, a C. elegans VCP homolog, repeatedly rotates clockwise and resets against the D2 ring. A similar result was obtained with human VCP. Based on these observations, we have proposed that repeated back and forward rotations of VCP may account for mechanical force in disaggregation.
All 2014 2013 2012 Other
All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (17 results) (of which Invited: 2 results) Book (2 results) Remarks (9 results)
Structure
Volume: 21 Issue: 11 Pages: 1992-2002
10.1016/j.str.2013.08.017
J Struct Biol.
Volume: 179 Issue: 2 Pages: 104-111
10.1016/j.jsb.2012.06.009
J. Struct. Biol.
Volume: (in press) Issue: 2 Pages: 143-151
10.1016/j.jsb.2012.04.022
Volume: (in press) Issue: 2 Pages: 138-142
10.1016/j.jsb.2012.04.010
Volume: (in press) Issue: 2 Pages: 112-120
10.1016/j.jsb.2012.04.017
http://mukb.medic.kumamoto-u.ac.jp/fukusei/index.html
http://mukb.medic.kumamoto-u.ac.jp/AAA/aaainfo.html
http://www.imeg.kumamoto-u.ac.jp/index.html