CheShift-2 resolves a local inconsistency between two X-ray crystal structures

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• 作者：Jorge A. Vila (12)
  Shih-Che Sue (34)
  James S. Fraser (5)
  Harold A. Scheraga (1)
  H. Jane Dyson (3) dyson@scripps.edu
• 关键词：Chemical shift &#8211 ; NFκ ; B &#8211 ; Iκ ; B &#8211 ; Structure validation
• 刊名：Journal of Biomolecular NMR
• 出版年：2012
• 出版时间：October 2012
• 年：2012
• 卷：54
• 期：2
• 页码：193-198
• 全文大小：434.6 KB
• 参考文献：1. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, Echols N, Headd JJ, Hung LW, Kapral GJ, Grosse-Kunstleve RW, McCoy AJ, Moriarty NW, Oeffner R, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, Zwart PH (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D 66:213–221
  2. Arnautova YA, Vila JA, Martin OA, Scheraga HA (2009) What can we learn by computing 13Calpha chemical shifts for X-ray protein models? Acta Crystallogr D 65:697–703
  3. Baeuerle PA (1998) IκB-NF-κB structures: at the interface of inflammation control. Cell 95:729–731
  4. Baeuerle PA, Baltimore D (1996) NF-κB: ten years after. Cell 87:13–20
  5. Baldwin AS (1996) The NF-κB and I-κB proteins: new discoveries and insights. Ann Rev Immunol 14:649–683
  6. Bergqvist S, Ghosh G, Komives EA (2008) The IκBα/NF-κB complex has two hot spots, one at either end of the interface. Protein Sci 17:2051–2058
  7. Bergqvist S, Alverdi V, Mengel B, Hoffmann A, Ghosh G, Komives EA (2009) Kinetic enhancement of NF-κB路DNA dissociation by IκBα. Proc Natl Acad Sci USA 106:19328–19333
  8. Bhattacharya A, Tejero R, Montelione GT (2007) Evaluating protein structures determined by structural genomics consortia. Proteins 66:778–795
  9. Chen FE, Huang DB, Chen YQ, Ghosh G (1998) Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA. Nature 391:410–413
  10. Emsley P, Lohkamp B, Scott WG, Cowtan K (2010) Features and development of coot. Acta Crystallogr D Biol Crystallogr 66:486–501
  11. Ernst MK, Dunn LL, Rice NR (1995) The PEST-like sequence of IkBα is responsible for inhibition of DNA binding but not for cytoplasmic retention of c-Rel or RelA homodimers. Mol Cell Biol 15:872–882
  12. Fraser JS, Clarkson MW, Degnan SC, Erion R, Kern D, Alber T (2009) Hidden alternative structures of proline isomerase essential for catalysis. Nature 462:669–673
  13. Han B, Liu Y, Ginzinger SW, Wishart DS (2011) SHIFTX2: significantly improved protein chemical shift prediction. J Biomol NMR 50:43–57
  14. Hayden MS, Ghosh S (2004) Signaling to NF-κB. Genes Dev 18:2195–2224
  15. Hayden MS, Ghosh S (2008) Shared principles in NF-κB signaling. Cell 132:344–362
  16. Huang YJ, Powers R, Montelione GT (2005) Protein NMR recall, precision, and F-measure scores (RPF scores): structure quality assessment measures based on information retrieval statistics. J Am Chem Soc 127:1665–1674
  17. Huxford T, Huang DB, Malek S, Ghosh G (1998) The crystal structure of the IκBα/NF-κB complex reveals mechanisms of NF-κB inactivation. Cell 95:759–770
  18. Jacobs MD, Harrison SC (1998) Structure of an IκBα/NF-κB complex. Cell 95:749–758
  19. Joosten RP, Joosten K, Murshudov GN, Perrakis A (2012) PDB_REDO: constructive validation, more than just looking for errors. Acta Crystallogr D Biol Crystallogr 68:484–496
  20. Karin M, Cao Y, Greten FR, Li ZW (2002) NF-κB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301–310
  21. Kumar S, Gelinas C (1993) IκBα-mediated inhibition of v-Rel DNA binding requires direct interaction with the RXXRXRXXC Rel/κB DNA-binding motif. Proc Natl Acad Sci USA 90:8962–8966
  22. Martin OA, Vila JA, Scheraga HA (2012) CheShift-2: graphic validation of protein structures. Bioinformatics 28:1538–1539
  23. Nabuurs SB, Spronk CAEM, Vuister GW, Vriend G (2006) Traditional biomolecular structure determination by NMR spectroscopy allows for major errors. PLoS Comput Biol 2:71–79
  24. Sen R, Baltimore D (1986) Inducibility of κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism. Cell 47:921–928
  25. Shen Y, Bax A (2007) Protein backbone chemical shifts predicted from searching a database for torsion angle and sequence homology. J Biomol NMR 38:289–302
  26. Sue SC, Dyson HJ (2009) Interaction of the IκBα C-terminal PEST sequence with NF-κB: insights into the inhibition of NF-κB DNA binding by IκBα. J Mol Biol 388:824–838
  27. Sue SC, Cervantes C, Komives EA, Dyson HJ (2008) Transfer of flexibility between ankyrin repeats in IκBα upon formation of the NF-κB complex. J Mol Biol 380:917–931
  28. Vila JA, Scheraga HA (2009) Assessing the accuracy of protein structures by quantum mechanical computations of 13C(alpha) chemical shifts. Acc Chem Res 42:1545–1553
• 作者单位：1. Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA2. IMASL-CONICET, Universidad Nacional de San Luis, Ej茅rcito de Los Andes, 950-5700 San Luis, Argentina3. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA4. Department of Life Sciences, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan5. California Institute of Quantitative Biosciences (QB3) and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
• ISSN：1573-5001

文摘

Since chemical shifts provide important and relatively accessible information about protein structure in solution, a Web server, CheShift-2, was developed for structure interrogation, based on a quantum mechanics database of 13C α chemical shifts. We report the application of CheShift-2 to a local inconsistency between two X-ray crystal structures (PDB IDs 1IKN and 1NFI) of the complex between the p65/p50 heterodimer of NFκB and its inhibitor IκBα. The availability of NMR resonance assignments that included the region of the inconsistency provided an opportunity for independent validation of the CheShift-2 server. Application of the server showed that the 13C α chemical shifts measured for the Gly270-Pro281 sequence close to the C-terminus of IκBα were unequivocally consistent with the backbone structure modeled in the 1IKN structure, and were inconsistent with the 1NFI structure. Previous NOE measurements had demonstrated that the position of a tryptophan ring in the region immediately N-terminal in this region was not consistent with either structure. Subsequent recalculation of the local structure in this region, based on the electron density of the deposited structure factors for 1IKN, confirmed that the local backbone structure was best modeled by 1IKN, but that the rotamer of Trp258 is consistent with the 1NFI structure, including the presence of a hydrogen bond between the ring NεH of Trp258 and the backbone carbonyl group of Gln278. The consensus between all of these measures suggests that the CheShift-2 server operates well under circumstances in which backbone chemical shifts are available but where local plasticity may render X-ray structural data ambiguous.