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PMID: 18275810 Published · ppublish English Evaluation Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

De novo high-resolution protein structure determination from sparse spin-labeling EPR data.

Structure (London, England : 1993) ·Vol. 16 ·No. 2 ·2008-02-00 ·Pages 181-95

Alexander N, Bortolus M, Al-Mestarihi A, Mchaourab H, Meiler J

Abstract

As many key proteins evade crystallization and remain too large for nuclear magnetic resonance spectroscopy, electron paramagnetic resonance (EPR) spectroscopy combined with site-directed spin labeling offers an alternative approach for obtaining structural information. Such information must be translated into geometric restraints to be used in computer simulations. Here, distances between spin labels are converted into distance ranges between beta carbons by using a "motion-on-a-cone" model, and a linear-correlation model links spin-label accessibility to the number of neighboring residues. This approach was tested on T4-lysozyme and alphaA-crystallin with the de novo structure prediction algorithm Rosetta. The results demonstrate the feasibility of obtaining highly accurate, atomic-detail models from EPR data by yielding 1.0 A and 2.6 A full-atom models, respectively. Distance restraints between amino acids far apart in sequence but close in space are most valuable for structure determination. The approach can be extended to other experimental techniques such as fluorescence spectroscopy, substituted cysteine accessibility method, or mutational studies.

MeSH Terms
Algorithms Electron Spin Resonance Spectroscopy Linear Models Models, Molecular Muramidase/chemistry Protein Conformation Protein Folding Spin Labels alpha-Crystallin A Chain/chemistry
Chemicals
Spin Labels alpha-Crystallin A Chain Muramidase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Alexander Nathan
Department of Chemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN 37212, USA.
Bortolus Marco
Al-Mestarihi Ahmad
Mchaourab Hassane
Meiler Jens
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
0969-2126
DOI
10.1016/j.str.2007.11.015
Published
2008-02-00
Pages
181-95
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC2390841
Subset
IM
Grants
NIGMS NIH HHS · T32 GM008320 · United States
NIGMS NIH HHS · T32 GM008320-19 · United States
NIGMS NIH HHS · R01 GM080403 · United States
NIGMS NIH HHS · R01 GM080403-01A1 · United States
NEI NIH HHS · R01 EY012683 · United States
NEI NIH HHS · R01 EY012683-10 · United States
NIGMS NIH HHS · R01-GM080403 · United States
NIGMS NIH HHS · T32 GM08320 · United States
NEI NIH HHS · R01-EY12683 · United States
External Links
PubMed source DOI: 10.1016/j.str.2007.11.015 PMC Full Text View journal details
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