• Users Online: 777
  • Home
  • Print this page
  • Email this page
INVITED REVIEW
Year : 2020  |  Volume : 15  |  Issue : 3  |  Page : 407-415

Navigating the dynamic landscape of alpha-synuclein morphology: a review of the physiologically relevant tetrameric conformation


Department of Chemistry, Virginia Commonwealth University, Richmond, VA, USA

Correspondence Address:
Heather R Lucas
Department of Chemistry, Virginia Commonwealth University, Richmond, VA
USA
Login to access the Email id

Source of Support: This work was supported in part by Award No. 18-7 (to HRL) from the Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Award Fund, administered by the Virginia Center on Aging, Conflict of Interest: None


DOI: 10.4103/1673-5374.265792

Rights and Permissions

N-acetylated α-synuclein (αSyn) has long been established as an intrinsically disordered protein associated with a dysfunctional role in Parkinson’s disease. In recent years, a physiologically relevant, higher order conformation has been identified as a helical tetramer that is tailored by buried hydrophobic interactions and is distinctively aggregation resistant. The canonical mechanism by which the tetramer assembles remains elusive. As novel biochemical approaches, computational methods, pioneering purification platforms, and powerful imaging techniques continue to develop, puzzling information that once sparked debate as to the veracity of the tetramer has now shed light upon this new counterpart in αSyn neurobiology. Nuclear magnetic resonance and computational studies on multimeric αSyn structure have revealed that the protein folding propensity is controlled by small energy barriers that enable large scale reconfiguration. Alternatively, familial mutations ablate tetramerization and reconfigure polymorphic fibrillization. In this review, we will discuss the dynamic landscape of αSyn quaternary structure with a focus on the tetrameric conformation.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed176    
    Printed0    
    Emailed0    
    PDF Downloaded61    
    Comments [Add]    

Recommend this journal