Electrostatic Repulsion Governs TDP-43 C-terminal Domain Aggregation

Miguel Mompeán; Avijit Chakrabartty; Emanuele Buratti; Douglas V Laurents

doi:10.1371/journal.pbio.1002447

Electrostatic Repulsion Governs TDP-43 C-terminal Domain Aggregation

PLoS Biol. 2016 Apr 20;14(4):e1002447. doi: 10.1371/journal.pbio.1002447. eCollection 2016 Apr.

Authors

Miguel Mompeán¹, Avijit Chakrabartty², Emanuele Buratti³, Douglas V Laurents¹

Affiliations

¹ Instituto de Química Física "Rocasolano" CSIC, Madrid, Spain.
² Department of Biochemistry, University of Toronto, Toronto Medical Discovery Tower 4-305, MaRS Centre, Toronto, Canada.
³ International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.

Abstract

TDP-43 is a protein that forms aggregates implicated in amyotrophic lateral sclerosis. In response to a recent study, this Formal Comment argues that the pH-dependent solubility of this protein is better explained by the mutual repulsion of charged groups than by the formation of hydrogen bonds.

Publication types

Research Support, Non-U.S. Gov't
Comment

MeSH terms

Amyotrophic Lateral Sclerosis / genetics*
DNA-Binding Proteins / metabolism*
Humans

Substances

DNA-Binding Proteins

Grants and funding

Supported by Grants SAF2013-49179-C2-2-R (DVL), EU Joint Programme-Neurodegenerative Diseases grants RiMod-FTD, Ministerio della Sanita' (EB), and AC14/00037 (DVL) & Thierry Latran Foundation (REHNPALS) (EB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.