Determination of the Structures of Symmetric Protein Oligomers from NMR Chemical Shifts and Residual Dipolar Couplings
Sgourakis, Nikolaos G. ; Lange, Oliver F. ; DiMaio, Frank ; André, Ingemar LU
; Fitzkee, Nicholas C.
; Rossi, Paolo
; Montelione, Gaetano T.
; Bax, Ad
and Baker, David
(2011)
In Journal of the American Chemical Society
133(16).
p.6288-6298
- Abstract
- Symmetric protein dimers, trimers, and higher-order cyclic oligomers play key roles in many biological processes. However, structural studies of oligomeric systems by solution NMR can be difficult due to slow tumbling of the system and the difficulty in identifying NOE interactions across protein interfaces. Here, we present an automated method (RosettaOligomers) for determining the solution structures of oligomeric systems using only chemical shifts, sparse NOEs, and domain orientation restraints from residual dipolar couplings (RDCs) without a need for a previously determined structure of the monomeric subunit. The method integrates previously developed Rosetta protocols for solving the structures of monomeric proteins using sparse NMR... (More)
- Symmetric protein dimers, trimers, and higher-order cyclic oligomers play key roles in many biological processes. However, structural studies of oligomeric systems by solution NMR can be difficult due to slow tumbling of the system and the difficulty in identifying NOE interactions across protein interfaces. Here, we present an automated method (RosettaOligomers) for determining the solution structures of oligomeric systems using only chemical shifts, sparse NOEs, and domain orientation restraints from residual dipolar couplings (RDCs) without a need for a previously determined structure of the monomeric subunit. The method integrates previously developed Rosetta protocols for solving the structures of monomeric proteins using sparse NMR data and for predicting the structures of both nonintertwined and intertwined symmetric oligomers. We illustrated the performance of the method using a benchmark set of nine protein dimers, one trimer, and one tetramer with available experimental data and various interface topologies. The final converged structures are found to be in good agreement with both experimental data and previously published high-resolution structures. The new approach is more readily applicable to large oligomeric systems than conventional structure-determination protocols, which often require a large number of NOEs, and will likely become increasingly relevant as more high-molecular weight systems are studied by NMR (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2094011
- author
- Sgourakis, Nikolaos G.
; Lange, Oliver F.
; DiMaio, Frank
; André, Ingemar
LU
; Fitzkee, Nicholas C.
; Rossi, Paolo
; Montelione, Gaetano T.
; Bax, Ad
and Baker, David
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of the American Chemical Society
- volume
- 133
- issue
- 16
- pages
- 6288 - 6298
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- wos:000292715500032
- scopus:79954990720
- pmid:21466200
- ISSN
- 1520-5126
- DOI
- 10.1021/ja111318m
- language
- English
- LU publication?
- yes
- id
- 30b0b20a-0bee-4f41-b117-fc822bfb98d9 (old id 2094011)
- date added to LUP
- 2016-04-01 13:02:21
- date last changed
- 2022-01-27 08:57:11
@article{30b0b20a-0bee-4f41-b117-fc822bfb98d9,
abstract = {{Symmetric protein dimers, trimers, and higher-order cyclic oligomers play key roles in many biological processes. However, structural studies of oligomeric systems by solution NMR can be difficult due to slow tumbling of the system and the difficulty in identifying NOE interactions across protein interfaces. Here, we present an automated method (RosettaOligomers) for determining the solution structures of oligomeric systems using only chemical shifts, sparse NOEs, and domain orientation restraints from residual dipolar couplings (RDCs) without a need for a previously determined structure of the monomeric subunit. The method integrates previously developed Rosetta protocols for solving the structures of monomeric proteins using sparse NMR data and for predicting the structures of both nonintertwined and intertwined symmetric oligomers. We illustrated the performance of the method using a benchmark set of nine protein dimers, one trimer, and one tetramer with available experimental data and various interface topologies. The final converged structures are found to be in good agreement with both experimental data and previously published high-resolution structures. The new approach is more readily applicable to large oligomeric systems than conventional structure-determination protocols, which often require a large number of NOEs, and will likely become increasingly relevant as more high-molecular weight systems are studied by NMR}},
author = {{Sgourakis, Nikolaos G. and Lange, Oliver F. and DiMaio, Frank and André, Ingemar and Fitzkee, Nicholas C. and Rossi, Paolo and Montelione, Gaetano T. and Bax, Ad and Baker, David}},
issn = {{1520-5126}},
language = {{eng}},
number = {{16}},
pages = {{6288--6298}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Journal of the American Chemical Society}},
title = {{Determination of the Structures of Symmetric Protein Oligomers from NMR Chemical Shifts and Residual Dipolar Couplings}},
url = {{http://dx.doi.org/10.1021/ja111318m}},
doi = {{10.1021/ja111318m}},
volume = {{133}},
year = {{2011}},
}