Baker, M.L., Jiang, W., Wedemeyer, W.J., Rixon, F.J., Baker, D. and Chiu, W. (2006) Ab initio modeling of the herpesvirus VP26 core domain assessed by CryoEM density. PLoS Computational Biology, 2(10), e146. (doi: 10.1371/journal.pcbi.0020146) (PMID:17069457) (PMCID:PMC1626159)
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Abstract
Efforts in structural biology have targeted the systematic determination of all protein structures through experimental determination or modeling. In recent years, 3-D electron cryomicroscopy (CryoEM) has assumed an increasingly important role in determining the structures of these large macromolecular assemblies to intermediate resolutions (6-10 A). While these structures provide a snapshot of the assembly and its components in well-defined functional states, the resolution limits the ability to build accurate structural models. In contrast, sequence-based modeling techniques are capable of producing relatively robust structural models for isolated proteins or domains. In this work, we developed and applied a hybrid modeling approach, utilizing CryoEM density and ab initio modeling to produce a structural model for the core domain of a herpesvirus structural protein, VP26. Specifically, this method, first tested on simulated data, utilizes the CryoEM density map as a geometrical constraint in identifying the most native-like models from a gallery of models generated by ab initio modeling. The resulting model for the core domain of VP26, based on the 8.5-A resolution herpes simplex virus type 1 (HSV-1) capsid cryoEM structure and mutational data, exhibited a novel fold. Additionally, the core domain of VP26 appeared to have a complementary interface to the known upper-domain structure of VP5, its cognate binding partner. While this new model provides for a better understanding of the assembly and interactions of VP26 in HSV-1, the approach itself may have broader applications in modeling the components of large macromolecular assemblies.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Rixon, Dr Frazer |
| Authors: | Baker, M.L., Jiang, W., Wedemeyer, W.J., Rixon, F.J., Baker, D., and Chiu, W. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | PLoS Computational Biology |
| Publisher: | Public Library of Science |
| ISSN: | 1553-734X |
| ISSN (Online): | 1553-7358 |
| Published Online: | 27 September 2006 |
| Copyright Holders: | Copyright © 2006 The Authors |
| First Published: | First published in PLoS ONE 2(10):e146 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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