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Exploring alternate states and oligomerization preferences of coiled-coils by de novo structure modeling

Rämisch, Sebastian LU ; Lizatovic, Robert LU and André, Ingemar LU (2015) In Proteins 83(2). p.235-247
Abstract
Homomeric coiled-coils can self-assemble into a wide range of structural states with different helix topologies and oligomeric states. In this study, we have combined de novo structure modeling with stability calculations to simultaneously predict structure and oligomeric states of homomeric coiled-coils. For dimers an asymmetric modeling protocol was developed. Modeling without symmetry constraints showed that backbone asymmetry is important for the formation of parallel dimeric coiled-coils. Collectively, our results demonstrate that high-resolution structure of coiled-coils, as well as parallel and antiparallel orientations of dimers and tetramers, can be accurately predicted from sequence. De novo modeling was also used to generate... (More)
Homomeric coiled-coils can self-assemble into a wide range of structural states with different helix topologies and oligomeric states. In this study, we have combined de novo structure modeling with stability calculations to simultaneously predict structure and oligomeric states of homomeric coiled-coils. For dimers an asymmetric modeling protocol was developed. Modeling without symmetry constraints showed that backbone asymmetry is important for the formation of parallel dimeric coiled-coils. Collectively, our results demonstrate that high-resolution structure of coiled-coils, as well as parallel and antiparallel orientations of dimers and tetramers, can be accurately predicted from sequence. De novo modeling was also used to generate models of competing oligomeric states, which were used to compare stabilities and thus predict the native stoichiometry from sequence. In a benchmark set of 33 coiled-coil sequences, forming dimers to pentamers, up to 70% of the oligomeric states could be correctly predicted. The calculations demonstrated that the free energy of helix folding could be an important factor for determining stability and oligomeric state of homomeric coiled-coils. The computational methods developed here should be broadly applicable to studies of sequence-structure relationships in coiled-coils and the design of higher order assemblies with improved oligomerization specificity. This article is protected by copyright. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proteins
volume
83
issue
2
pages
235 - 247
publisher
John Wiley & Sons
external identifiers
  • pmid:25402423
  • wos:000348724500004
  • scopus:84924783388
ISSN
0887-3585
DOI
10.1002/prot.24729
language
English
LU publication?
yes
id
af29e39a-42b9-427d-9d5a-b66a56e376ba (old id 4816474)
date added to LUP
2014-12-12 14:53:23
date last changed
2017-07-23 03:10:04
@article{af29e39a-42b9-427d-9d5a-b66a56e376ba,
  abstract     = {Homomeric coiled-coils can self-assemble into a wide range of structural states with different helix topologies and oligomeric states. In this study, we have combined de novo structure modeling with stability calculations to simultaneously predict structure and oligomeric states of homomeric coiled-coils. For dimers an asymmetric modeling protocol was developed. Modeling without symmetry constraints showed that backbone asymmetry is important for the formation of parallel dimeric coiled-coils. Collectively, our results demonstrate that high-resolution structure of coiled-coils, as well as parallel and antiparallel orientations of dimers and tetramers, can be accurately predicted from sequence. De novo modeling was also used to generate models of competing oligomeric states, which were used to compare stabilities and thus predict the native stoichiometry from sequence. In a benchmark set of 33 coiled-coil sequences, forming dimers to pentamers, up to 70% of the oligomeric states could be correctly predicted. The calculations demonstrated that the free energy of helix folding could be an important factor for determining stability and oligomeric state of homomeric coiled-coils. The computational methods developed here should be broadly applicable to studies of sequence-structure relationships in coiled-coils and the design of higher order assemblies with improved oligomerization specificity. This article is protected by copyright. All rights reserved.},
  author       = {Rämisch, Sebastian and Lizatovic, Robert and André, Ingemar},
  issn         = {0887-3585},
  language     = {eng},
  number       = {2},
  pages        = {235--247},
  publisher    = {John Wiley & Sons},
  series       = {Proteins},
  title        = {Exploring alternate states and oligomerization preferences of coiled-coils by de novo structure modeling},
  url          = {http://dx.doi.org/10.1002/prot.24729},
  volume       = {83},
  year         = {2015},
}