Journal article
Cryo-EM of the pathogenic VCP variant R155P reveals long-range conformational changes in the D2 ATPase ring
D Mountassif, L Fabre, Y Zaid, D Halawani, I Rouiller
Biochemical and Biophysical Research Communications | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2015
Abstract
Single amino acid mutations in valosin containing protein (VCP/p97), a highly conserved member of the ATPases associated with diverse cellular activities (AAA) family of ATPases has been linked to a severe degenerative disease affecting brain, muscle and bone tissue. Previous studies have demonstrated the role of VCP mutations in altering the ATPase activity of the D2 ring; however the structural consequences of these mutations remain unclear. In this study, we report the three-dimensional (3D) map of the pathogenic VCP variant, R155P, as revealed by single-particle Cryo-Electron Microscopy (EM) analysis at 14 Å resolution. We show that the N-terminal R155P mutation induces a large structura..
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Awarded by Canadian Institutes of Health Research
Funding Acknowledgements
This work was supported by operating grants to I.R. from the Canadian Institutes of Health Research (CIHR reference number 86693MOP). I.R. received a CIHR New Investigator award. The Canadian Foundation for Innovation provided infrastructure. The Facility for Electron Microscopy Research at McGill University (FEMR) provided technical support and access to equipment. This work was facilitated by computing resources from CLUMEQ under Compute/Calcul Canada.