Abstract
This ‘Perspective’ bears on the present state of protein structure determination by NMR in solution. The focus is on a comparison of the infrastructure available for NMR structure determination when compared to protein crystal structure determination by X-ray diffraction. The main conclusion emerges that the unique potential of NMR to generate high resolution data also on dynamics, interactions and conformational equilibria has contributed to a lack of standard procedures for structure determination which would be readily amenable to improved efficiency by automation. To spark renewed discussion on the topic of NMR structure determination of proteins, procedural steps with high potential for improvement are identified.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Notes
Quotation from the “Report of the Protein Structure Initiative Assessment Panel” (http://www.nigms.nih.gov/News/Reports/PSIAssessmentPanel2007.htm). “A.3.2C NMR. NMR technology from the PSI is not seen as having the general impact described above for crystallography. Many of the NMR advances (G-matrix Fourier-transform NMR, automated data analysis and structure determination) are not readily applicable to complex systems with higher molecular weight. Thus, these have not changed the practices of the NMR community in the way PSI-supported technologies have changed the crystallographic community.”
References
Acton TB, Gunsalus KC, Xiao R, Ma LC, Aramini J, Baran MC, Chiang Y-W, Climent T, Cooper B, Denissova NG, Douglas SM, Everett JK, Ho CK, Macapagal D, Rajan PK, Shastry R, Shih L-Y, Swapna GV, Wilson M, Wu M, Gerstein M, Inouye M, Hunt JF, Montelione GT (2005) Robotic cloning and protein production platform of the northeast structural genomics consortium. Methods Enzymol 394:210–243
Bagby S, Tong KI, Liu D, Alattia JR, Ikura M (1997) The button test: a small scale method using microdialysis cells for assessing protein solubility at concentrations suitable for NMR. J Biomol NMR 10:279–282
Bagby S, Tong KI, Ikura M (2001) Optimization of protein solubility and stability for protein nuclear magnetic resonance. Methods Enzymol 339:20–41
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN (2000) The protein data bank. Nucleic Acids Res 28:235–242
Bhattacharya A, Tejero R, Montelione G (2007) Evaluating protein structures determined by structural genomics consortia. Proteins 66:778–795
Brown EN, Ramaswamy S (2007) Quality of protein crystal structures. Acta Crystallogr D 63:941–950
Cavanagh J, Fairbrother WJ, Palmer AG, Rance M, Skelton NJ (2007) Protein NMR spectroscopy. Academic Press, New York
Chandonia J-M, Brenner SE (2006) The impact of structural genomics: expectations and outcomes. Science 311:347–351
Levitt M (2007) Growth of novel protein structural data. Proc Natl Acad Sci USA 104:3183–3188
Liu G, Shen Y, Atreya HS, Parish D, Shao Y, Sukumaran DK, Xiao R, Yee A, Lemak A, Bhattacharya A, Acton TA, Arrowsmith CH, Montelione GT, Szyperski T (2005) NMR data collection and analysis protocol for high-throughput protein structure determination. Proc Natl Acad Sci USA 102:10487–10492
Pan X, Wesenberg GE, Markley JL, Fox BG, Phillips GN Jr, Bingman CA (2007) A graphical approach to tracking and reporting target status in structural genomics. J Struct Funct Genomics 8:209–216
Slabinski L, Jaroszewski L, Rychlewski L, Wilson IA, Lesley SA, Godzik A (2007a) XtalPred: a web server for prediction of protein crystallizability. Bioinformatics 23:3403–3405
Slabinski L, Jaroszewski L, Rodrigues APC, Rychlewski L, Wilson IA, Lesley SA, Godzik A (2007b) The challenge of protein structure determination—lessons from structural genomics. Protein Sci 16:2472–2482
Stuart DI, Jones EY, Wilson KS, Daenke S (2006) Structural proteomics in Europe—the best of both worlds. Acta Crystallogr D. doi:10.1107/S0907444906035347
Wüthrich K (2003) NMR studies of structure and function of biological macromolecules. J Biomol NMR 27:13–39
Yee A, Chang X, Pineda-Lucena A, Wu B, Semsei A, Le B, Ramelot T, Lee GM, Bhattacharyya S, Gutierrez P, Denisov A, Lee C-H, Cort JR, Kozlov G, Liao J, Finak G, Chen L, Wishart D, Lee W, Mcintosh LP, Gerhring K, Kennedy MA, Edwards AM, Arrowsmith CH (2002) An NMR approach to structural proteomics. Proc Natl Acad Sci USA 99:1825–1830
Yokoyama S, Hirota H, Kigawa T, Yabuki T, Shirouzu M, Terada T, Ito Y, Matsuo Y, Kuroda Y, Nishimura Y, Kyogoku Y, Miki K, Masui R, Kuramitsu S (2002) Structural genomics projects in Japan. Nat Struct Biol 7:943–945
Acknowledgements
We thank Dr. Ian A. Wilson for a critical reading of the manuscript. M.B. acknowledges support by the EU (LSHG-CT-2005-018988), G.W. by the NIH grant GM 47467, and K.W. by the Joint Center for Structural Genomics in La Jolla, CA, USA (JCSG, NIH #GM074898) and the NCCR Structural Biology (Swiss National Science Foundation and ETH Zürich, Switzerland).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Billeter, M., Wagner, G. & Wüthrich, K. Solution NMR structure determination of proteins revisited. J Biomol NMR 42, 155–158 (2008). https://doi.org/10.1007/s10858-008-9277-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10858-008-9277-8