Document Detail

Structural characterization of components of protein assemblies by comparative modeling and electron cryo-microscopy.
MedLine Citation:
PMID:  15681235     Owner:  NLM     Status:  MEDLINE    
We explore structural characterization of protein assemblies by a combination of electron cryo-microscopy (cryoEM) and comparative protein structure modeling. Specifically, our method finds an optimal atomic model of a given assembly subunit and its position within an assembly by fitting alternative comparative models into a cryoEM map. The alternative models are calculated by MODELLER [J. Mol. Biol. 234 (1993) 313] from different sequence alignments between the modeled protein and its template structures. The fitting of these models into a cryoEM density map is performed either by FOLDHUNTER [J. Mol. Biol. 308 (2001) 1033] or by a new density fitting module of MODELLER (Mod-EM). Identification of the most accurate model is based on the correlation between the model accuracy and the quality of fit into the cryoEM density map. To quantify this correlation, we created a benchmark consisting of eight proteins of different structural folds with corresponding density maps simulated at five resolutions from 5 to 15 angstroms, with three noise levels each. Each of the proteins in the set was modeled based on 300 different alignments to their remotely related templates (12-32% sequence identity), spanning the range from entirely inaccurate to essentially accurate alignments. The benchmark revealed that one of the most accurate models can usually be identified by the quality of its fit into the cryoEM density map, even for noisy maps at 15 angstroms resolution. Therefore, a cryoEM density map can be helpful in improving the accuracy of a comparative model. Moreover, a pseudo-atomic model of a component in an assembly may be built better with comparative models of the native subunit sequences than with experimentally determined structures of their homologs.
Maya Topf; Matthew L Baker; Bino John; Wah Chiu; Andrej Sali
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of structural biology     Volume:  149     ISSN:  1047-8477     ISO Abbreviation:  J. Struct. Biol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-31     Completed Date:  2005-06-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9011206     Medline TA:  J Struct Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  191-203     Citation Subset:  IM    
Department of Biopharmaceutical Sciences, California Institute for Quantitative Biomedical Research, Mission Bay Genentech Hall, 600 16th Street, Suite N472D, University of California, San Francisco, CA 94143, USA.
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MeSH Terms
Cryoelectron Microscopy*
Models, Molecular*
Protein Conformation*
Sequence Alignment
Grant Support

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