Residue histidine 50 plays a key role in protecting α-Synuclein from aggregation at physiological pH

Abstract

Background: Mutations of α-synuclein (αSyn) can cause early-onset familial Parkinson disease (PD). Results: The H50Q, H50D, or H50A substitution promotes, whereas the H50R substitution inhibits, αSyn aggregation in vitro. Conclusion: The recently identified PD-causing αSyn mutant, αSyn(H50Q), accelerates αSyn aggregation. Significance: The partial positive charge of His-50 at physiological pH likely plays a role in suppressing αSyn aggregation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.