Document Detail


Solid-state NMR analysis of membrane proteins and protein aggregates by proton detected spectroscopy.
MedLine Citation:
PMID:  22986689     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Solid-state NMR has emerged as an important tool for structural biology and chemistry, capable of solving atomic-resolution structures for proteins in membrane-bound and aggregated states. Proton detection methods have been recently realized under fast magic-angle spinning conditions, providing large sensitivity enhancements for efficient examination of uniformly labeled proteins. The first and often most challenging step of protein structure determination by NMR is the site-specific resonance assignment. Here we demonstrate resonance assignments based on high-sensitivity proton-detected three-dimensional experiments for samples of different physical states, including a fully-protonated small protein (GB1, 6 kDa), a deuterated microcrystalline protein (DsbA, 21 kDa), a membrane protein (DsbB, 20 kDa) prepared in a lipid environment, and the extended core of a fibrillar protein (α-synuclein, 14 kDa). In our implementation of these experiments, including CONH, CO(CA)NH, CANH, CA(CO)NH, CBCANH, and CBCA(CO)NH, dipolar-based polarization transfer methods have been chosen for optimal efficiency for relatively high protonation levels (full protonation or 100 % amide proton), fast magic-angle spinning conditions (40 kHz) and moderate proton decoupling power levels. Each H-N pair correlates exclusively to either intra- or inter-residue carbons, but not both, to maximize spectral resolution. Experiment time can be reduced by at least a factor of 10 by using proton detection in comparison to carbon detection. These high-sensitivity experiments are especially important for membrane proteins, which often have rather low expression yield. Proton-detection based experiments are expected to play an important role in accelerating protein structure elucidation by solid-state NMR with the improved sensitivity and resolution.
Authors:
Donghua H Zhou; Andrew J Nieuwkoop; Deborah A Berthold; Gemma Comellas; Lindsay J Sperling; Ming Tang; Gautam J Shah; Elliott J Brea; Luisel R Lemkau; Chad M Rienstra
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-18
Journal Detail:
Title:  Journal of biomolecular NMR     Volume:  -     ISSN:  1573-5001     ISO Abbreviation:  J. Biomol. NMR     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9110829     Medline TA:  J Biomol NMR     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Physics, Oklahoma State University, Stillwater, OK, 74074, USA, donghua@okstate.edu.
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