Document Detail


Residue His50 Plays a Key Role in Protecting alpha-Synuclein from Aggregation at Physiological pH.
MedLine Citation:
PMID:  24742669     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
αSyn aggregation is involved in the pathogenesis of PD. Recently, substitution of histidine 50 in αSyn with a glutamine, H50Q, was identified as a new familial PD mutant. Here, nuclear magnetic resonance (NMR) studies revealed that the H50Q substitution causes an increase of the flexibility of the C-terminal region. This finding provides direct evidence that this PD-causing mutant can mediate long-range effects on the sampling of αSyn conformations. In vitro aggregation assays showed that substitution of His50 with Gln(Q), Asp(D) or Ala(A) promotes αSyn aggregation, whereas substitution with the positively-charged Arg suppresses αSyn aggregation. Histidine carries a partial positive charge at neutral pH, and so our result suggests that positively-charged His50 plays a role in protecting αSyn from aggregation under physiological conditions.
Authors:
Ying-Chih Chi; Geoffrey S Armstrong; David N M Jones; Elan Z Eisenmesser; Chang-Wei Liu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-4-17
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2014 Apr 
Date Detail:
Created Date:  2014-4-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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