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

Solid-state NMR;protein structure determination;fibrils;GB1;alpha synuclein;Parkinson’s disease;TEDOR;proton detection;nuclear magnetic resonance (NMR)

Nieuwkoop, Andrew

关键词: Solid-state NMR;    protein structure determination;    fibrils;    GB1;    alpha synuclein;    Parkinson’s disease;    TEDOR;    proton detection;    nuclear magnetic resonance (NMR);   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/29544/Nieuwkoop_Andrew.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Solid state NMR (SSNMR) is a structure determination technique uniquely suited tostudy protein aggregates and fibrils. Unlike solution NMR or X-ray crystallography,SSNMR can obtain atomic resolution structural information on samples of protein fibrilswhich are insoluble and do not produce X-ray diffracting crystals. As SSNMR begins torealize this potential, new structure determination techniques will be important in enableSSNMR to investigate ever larger and more complicated systems.Alpha-synuclein (AS) is the primary protein component of Lewy bodies, thepathological hallmark of Parkinson’s disease. The structure of AS in its fibril form isunknown, as is the mechanism by which it contributes to neurodegeneration. At 140residues, 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 withadvanced isotopic labeling schemes, and novel structure calculation methods. Thetechniques developed in this study will be useful in the study of other proteinaggregates, as well as membrane proteins and complexes, for which SSNMR is thestructure determination method of choice.