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Localized reconstruction of subunits from electron cryomicroscopy images of macromolecular complexes

Abstract:
Electron cryomicroscopy can yield near-atomic resolution structures of highly ordered macromolecular complexes. Often however some subunits bind in a flexible manner, have different symmetry from the rest of the complex, or are present in sub-stoichiometric amounts, limiting the attainable resolution. Here we report a general method for the localized three-dimensional reconstruction of such subunits. After determining the particle orientations, local areas corresponding to the subunits can be extracted and treated as single particles. We demonstrate the method using three examples including a flexible assembly and complexes harbouring subunits with either partial occupancy or mismatched symmetry. Most notably, the method allows accurate fitting of the monomeric RNA-dependent RNA polymerase bound at the threefold axis of symmetry inside a viral capsid, revealing for the first time its exact orientation and interactions with the capsid proteins. Localized reconstruction is expected to provide novel biological insights in a range of challenging biological systems.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/ncomms9843

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author


Publisher:
Nature Publishing Group
Journal:
Nature Communications More from this journal
Volume:
6
Article number:
8843
Publication date:
2015-11-04
Acceptance date:
2015-10-08
DOI:
EISSN:
2041-1723
ISSN:
2041-1723


Language:
English
Keywords:
Pubs id:
pubs:575131
UUID:
uuid:f577caf5-f8b6-49c4-83ad-e2ddc3e3ecab
Local pid:
pubs:575131
Source identifiers:
575131
Deposit date:
2016-04-22

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