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

Nieuwkoop, Andrew

Permalink

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

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

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

Owning Collections