University of Illinois Urbana-Champaign

Structure determination of proteins and protein aggregates by magic-angle spinning solid-state NMR

Nieuwkoop, Andrew

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https://hdl.handle.net/2142/29544

Description

Title
Structure determination of proteins and protein aggregates by magic-angle spinning solid-state NMR
Author(s)
Nieuwkoop, Andrew
Issue Date
2012-02-01T00:54:45Z
Director of Research (if dissertation) or Advisor (if thesis)
Rienstra, Chad M.
Committee Member(s)
  • Oldfield, Eric
  • Schulten, Klaus J.
  • George, Julia M.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2012-02-01T00:54:45Z
Keyword(s)
  • Solid-state NMR
  • protein structure determination
  • fibrils
  • GB1
  • alpha synuclein
  • Parkinson’s disease
  • TEDOR
  • proton detection
  • nuclear magnetic resonance (NMR)
Abstract
Solid state NMR (SSNMR) is a structure determination technique uniquely suited to study protein aggregates and fibrils. Unlike solution NMR or X-ray crystallography, SSNMR can obtain atomic resolution structural information on samples of protein fibrils which are insoluble and do not produce X-ray diffracting crystals. As SSNMR begins to realize this potential, new structure determination techniques will be important in enable SSNMR to investigate ever larger and more complicated systems. Alpha-synuclein (AS) is the primary protein component of Lewy bodies, the pathological hallmark of Parkinson’s disease. The structure of AS in its fibril form is unknown, as is the mechanism by which it contributes to neurodegeneration. At 140 residues, AS is much larger than other fibril systems that have been studied by SSNMR. To solve the structure of AS fibrils will require combining new pulse sequences with advanced isotopic labeling schemes, and novel structure calculation methods. The techniques developed in this study will be useful in the study of other protein aggregates, as well as membrane proteins and complexes, for which SSNMR is the structure determination method of choice.
Graduation Semester
2011-12
Permalink
http://hdl.handle.net/2142/29544
Copyright and License Information
Copyright 2011 Andrew Nieuwkoop

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