TY - JOUR
T1 - Structural NMR of protein oligomers using hybrid methods
AU - Wang, Xu
AU - Lee, Hsiau Wei
AU - Liu, Yizhou
AU - Prestegard, James H.
N1 - Funding Information:
We are grateful to Bruker AXS for use of their NANOSTAR system and to Brian Jones for help with collecting and evaluating the bioSAXS data on wild type CCL5, to Joshua Sharp & Caroline Watson of University of Georgia for performing the ion mobility MS experiment on wild type CCL5, and to Michael Kennedy of the Miami University for sharing his experiences with DEER data. We also acknowledge the National Center for Research Resources (a part of the NIH) for financial support of the Resource for Integrated Glycotechnology and the CCL5 project ( P41-RR005351 ), the National Institute of General Medical Sciences Protein Structure Initiative for support of H.-W.L. and Y.L. as a part of the NESG consortium (U54-GM074958, G.T. Montelione, PI), and the National Institute of General Medical Sciences K99 program for support of X.W. ( K99GM088483 ). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
PY - 2011/3
Y1 - 2011/3
N2 - Solving structures of native oligomeric protein complexes using traditional high-resolution NMR techniques remains challenging. However, increased utilization of computational platforms, and integration of information from less traditional NMR techniques with data from other complementary biophysical methods, promises to extend the boundary of NMR-applicable targets. This article reviews several of the techniques capable of providing less traditional and complementary structural information. In particular, the use of orientational constraints coming from residual dipolar couplings and residual chemical shift anisotropy offsets are shown to simplify the construction of models for oligomeric complexes, especially in cases of weak homo-dimers. Combining this orientational information with interaction site information supplied by computation, chemical shift perturbation, paramagnetic surface perturbation, cross-saturation and mass spectrometry allows high resolution models of the complexes to be constructed with relative ease. Non-NMR techniques, such as mass spectrometry, EPR and small angle X-ray scattering, are also expected to play increasingly important roles by offering alternative methods of probing the overall shape of the complex. Computational platforms capable of integrating information from multiple sources in the modeling process are also discussed in the article. And finally a new, detailed example on the determination of a chemokine tetramer structure will be used to illustrate how a non-traditional approach to oligomeric structure determination works in practice.
AB - Solving structures of native oligomeric protein complexes using traditional high-resolution NMR techniques remains challenging. However, increased utilization of computational platforms, and integration of information from less traditional NMR techniques with data from other complementary biophysical methods, promises to extend the boundary of NMR-applicable targets. This article reviews several of the techniques capable of providing less traditional and complementary structural information. In particular, the use of orientational constraints coming from residual dipolar couplings and residual chemical shift anisotropy offsets are shown to simplify the construction of models for oligomeric complexes, especially in cases of weak homo-dimers. Combining this orientational information with interaction site information supplied by computation, chemical shift perturbation, paramagnetic surface perturbation, cross-saturation and mass spectrometry allows high resolution models of the complexes to be constructed with relative ease. Non-NMR techniques, such as mass spectrometry, EPR and small angle X-ray scattering, are also expected to play increasingly important roles by offering alternative methods of probing the overall shape of the complex. Computational platforms capable of integrating information from multiple sources in the modeling process are also discussed in the article. And finally a new, detailed example on the determination of a chemokine tetramer structure will be used to illustrate how a non-traditional approach to oligomeric structure determination works in practice.
KW - CCL5
KW - Chemokines
KW - Dimers
KW - Protein structure
KW - Residual dipolar coupling
KW - SAXS
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U2 - 10.1016/j.jsb.2010.11.005
DO - 10.1016/j.jsb.2010.11.005
M3 - Article
C2 - 21074622
AN - SCOPUS:79851510775
SN - 1047-8477
VL - 173
SP - 515
EP - 529
JO - Journal of Structural Biology
JF - Journal of Structural Biology
IS - 3
ER -