Structural analysis of non-native states of proteins by NMR methods

Current Opinion in Structural Biology

Volumn 6, Issue 1, 1996, Pages 24-30

  Shortle, David R ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA LACTALBUMIN; APROTININ; BACTERIAL ENZYME; CYTOCHROME C; LYSOZYME; NITROGEN 15; NUCLEASE;

ALPHA HELIX; CARBON NUCLEAR MAGNETIC RESONANCE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DENATURATION; PROTEIN FOLDING; PROTEIN STRUCTURE; PROTON NUCLEAR MAGNETIC RESONANCE; REVIEW; STAPHYLOCOCCUS;

BACTERIA (MICROORGANISMS); STAPHYLOCOCCUS;

EID: 0029961647     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-440X(96)80091-1     Document Type: Article

References (58)

1. Van Halbeek H: NMR developments in structural studies of carbohydrates and their complexes. Curr Opin Struct Biol 1994, 4:697-709.
2. Wüthrich K: NMR assignments as a basis for structural characterization of denatured states of globular proteins. Curr Opin Struct Biol 1994, 4:93-99.
3. Bax A: Multidimensional nuclear magnetic resonance methods for protein studies. Curr Opin Struct Biol 1994, 4:738-744.
4. 15N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects. J Biomol NMR 1995, 5:67-81.
5. 15N 'random coil' chemical shifts. J Am Chem Soc 1994, 116:8466-8469.
6. 1H NMR assignments for the amino-terminal domain of the phage 434 repressor in the urea-unfolded form. Proc Natl Acad Sci USA 1992, 89:4397-4401.
7. Wang Y, Shortle D: The equilibrium folding pathway of staphylococcal nuclease: identification of the most stable chain-chain interactions. Biochemistry 1995, 34:in press. Evidence is presented for a stable but dynamic three-strand β sheet in a highly unfolded state of this protein. The unusual stability of this β meander correlates with the burial of a large amount of non-polar surface upon formation, and appears to depend on a local non-native interaction involving four large hydrophobic residues. From circular dichroism and NMR studies of this protein at various concentrations of glycerol [8] and urea, a specific hierarchical pattern of structure condensation is proposed for this protein, with the most stable structure at the N terminus and the least stable at the C terminus.
8. Wang Y, Alexandrescu AT, Shortle D: Initial studies of the equilibrium folding pathway of staphylococcal nuclease. Philos Trans R Soc Lond Biol 1995, 348:27-34.
9. 15N resonance assignments of the N-terminal SH3 domain of drk in folded and unfolded states using enhanced-sensitivity pulsed field gradient NMR techniques. J Biomol NMR 1994, 4:845-858.
10. Logan TM, Olejniczak ET, Xu RX, Fesik SW: A general method for assigning NMR spectra of denatured proteins using 3D HC(CO)NH-TOCSY triple resonance experiments. J Biomol NMR 1993, 3:225-231.
11. Alexandrescu AT, Abeygunawardana C, Shortle D: Structure and dynamics of a denatured 131-residue fragment of staphylococcal nuclease: a heteronuclear NMR study. Biochemistry 1994, 33:1063-1072.
12. 1H NMR assignments of its pH-denatured state. Proc Natl Acad Sci USA 1994, 91:9412-9416.
13. Englander SW, Mayne L: Protein folding studied using hydrogen-exchange labeling and two-dimensional NMR. Annu Rev Biophys Biomol Struc 1992, 21:243-265.
14. Bai Y, Sosnick TR, Mayne L, Englander SW: Protein folding intermediates: native-state hydrogen exchange. Science 1995, 269:192-197. Describes a remarkably simple strategy for defining and characterizing high-energy forms of the native state that have undergone partial structure breakdown but have not reached the transition state for unfolding. Results with cytochrome c are consistent with a series of local disruptions of progressively greater amounts of structure.
15. 15N correlation spectrum as a function of mixing time will be published soon.
16. Bai Y, Milne JS, Mayne L, Englander SW: Primary structure effects on peptide group hydrogen exchange. Proteins 1993, 17:75-86.
17. 15N chemical shifts are carefully quantified.
18. Buck M, Radford SE, Dobson CM: Amide hydrogen exchange in a highly denatured state - hen egg-white lysozyme in urea. J Mol Biol 1994, 237:247-254.
19. 1H chemical shifts obtained as a function of temperature and trifluoroethanol concentration for the peptide series GGXGG. J Biomol NMR 1995, 5:14-24.
20. Shortle D, Abeygunawardana C: NMR analysis of the residual structure in the denatured state of an unusual mutant of staphylococcal nuclease. Structure 1993, 1:121-134.
21. Redfield C, Smith RAG, Dobson CM: Structural characterization of a highly-ordered 'molten globule' at low pH. Nature Struct Biol 1994, 1:23-29. This non-native state, if it can be called that, represents the smallest reported unit of protein structure to break down in a cooperative reaction. These results, together with others described in this review, clearly suggest that the manner in which native structure breaks apart varies extensively among proteins and for the same protein subjected to different perturbations.
22. 13C nuclear magnetic resonance chemical shifts. J Am Chem Soc 1991, 113:5490-5492.
23. Wishart DS, Sykes BD, Richards FM: Relationship between nuclear magnetic resonance chemical shift and protein secondary structure. J Mol Biol 1991, 222:311-333.
24. Wishart DS, Sykes BD: Chemical shifts as a tool for structure determination. Methods Enzymol 1994, 239:363-392. An important reference on secondary shifts, this review covers all aspects of measuring and interpreting chemical shifts.
25. Reily MD, Thanabal V, Omecinsky DO: Structure-induced carbon-13 chemical shifts: a sensitive measure of transient localized secondary structure in peptides. J Am Chem Soc 1992, 114:6251-6252.
26. Alexandrescu AT, Gittis AG, Abeygunawardana C, Shortle D: NMR structure of a stable 'OB-fold' sub-domain isolated from staphylococcal nuclease. J Mol Biol 1995, 250:134-143. A subdomain within a single domain protein is stabilized, not by a disulfide bond [49•,50•] but by a glycine to valine substitution. This stable subdomain corresponds closely with a common structural motif, the OB domain. The authors speculate that the evolution of wild-type nuclease required loss of folding autonomy of the OB subdomain and its integration into a single, larger cooperative unit.
27. 15N relaxation measurements reveal large differences in the motions of different segments within this highly unfolded state. Some of the theoretical difficulties of interpreting such relaxation data when there is no single rotational correlation time are described.
28. Farrow NA, Zhang O, Forman-Kay JD, Kay LE: Comparison of the backbone dynamics of a folded and an unfolded SH3 domain existing in equilibrium in aqueous buffer. Biochemistry 1995, 34:868-878. Describes what may be the best protein system so far for characterizing the denatured state under native conditions.
29. Altieri AS, Hinton DP, Byrd RA: Association of biomolecular systems via pulsed field gradient NMR self-diffusion measurements. J Am Chem Soc 1995, 117:7566-7567. A simple NMR method for measuring the Stokes radius of non-native states and for assessing the aggregation state of folded or unfolded proteins. High sensitivity should permit measurements at concentrations at least as low as 0.1 mM protein.
30. Broadhurst RW, Dobson CM, Hore PS, Radford SE, Rees ML: A photochemically induced dynamic nuclear polarization study of denatured states of lysozyme. Biochemistry 1991, 30:405-412.
31. Esposito G, Lesk AM, Molinari H, Motta A, Niccolai N, Pastore A: Probing protein structure by solvent perturbation of nuclear magnetic resonance spectra. Nuclear magnetic resonance spectral editing and topological mapping in proteins by paramagnetic relaxation filtering. J Mol Biol 1992, 224:659-670.
32. Kosen PA: Spin labeling of proteins. Methods Enzymol 1989, 177:86-121.
33. Dotsch V, Wider G, Siegal G, Wüthrich K: Interaction of urea with an unfolded protein, the DNA-binding domain of the 434-repressor. FEBS Lett 1995, 366:6-10.
34. Jacobs MD, Fox RO: Staphylococcal nuclease folding intermediate characterized by hydrogen exchange and NMR spectroscopy. Proc Natl Acad Sci USA 1994, 91:449-453.
35. Kuwajima K: The molten globule as a clue for understanding the folding and cooperativity of globular protein structures. Proteins 1989, 6:87-103.
36. Dobson CM, Evans PA, Radford SE: Understanding how proteins fold: the lysozyme story so far. Trends Biochem Sci 1994, 19:31-37.
37. Alexandrescu AT, Ng YL, Dobson CM: Characterization of a trifluoroethanol-induced partially folded state of α-lactalbumin. J Mol Biol 1994, 235:587-599.
38. Smith LJ, Alexandrescu AT, Pitkeathly M, Dobson CM: Solution structure of a peptide fragment of human α-lactalbumin in trifluoroethanol: a model for local structure in the molten globule. Structure 1994, 2:703-712.
39. Wu LC, Peng ZY, Kim PS: Bipartite structure of the α-lactalbumin molten globule. Nature Struct Biol 1994 2:281-286.
40. Balbach J, Forge V, Van Nuland NAJ, Winder SL, Hore PJ, Dobson CM: Following protein folding in real time using NMR spectroscopy. Nature Struct Biol 1996, in press. A convincing demonstration that a protein folding reaction, if slow enough, can be monitored by a time series of 1D proton NMR spectra.
41. Kotik M, Radford SE, Dobson CM: Comparison of the refolding of hen lysozyme from dimethyl sulfoxide and guanidinium chloride. Biochemistry 1995, 34:1714-1724.
42. Jeng MF, Englander SW, Elove GA, Wand AJ, Roder H: Structural description of acid-denatured cytochrome c by hydrogen exchange and 2D NMR. Biochemistry 1990, 29:10433-10437.
43. Kuroda Y, Endo S, Nagayama K, Wada A: Stability of α-helices in a molten globule state of cytochrome c by hydrogen-deuterium exchange and two-dimensional NMR spectroscopy. J Mol Biol 1995, 247:682-688.
44. Sanz JM, Johnson CM, Fersht AR: The A-state of barnase. Biochemistry 1994, 33:11189-11199.
45. Kippen AD, Arcus VL, Fersht AR: Structural studies on peptides corresponding to mutants of the major α-helix of barnase. Biochemistry 1994, 33:10013-10021.
46. Kippen AD, Fersht AR: Analysis of the mechanism of assembly of cleaved barnase from two peptide fragments and its relevance to the folding pathway of uncleaved barnase. Biochemistry 1995, 34:1464-1468.
47. Zhang O, Forman-Kay JD: Structural characterization of folded and unfolded states of an SH3 domain in equilibrium in aqueous buffer. Biochemistry 1995, 34:6784-6794. A thorough search for residual secondary structure in this small denatured protein uncovers evidence for two segments that form dynamic structures different from those seen in the native state.
48. Lumb KJ, Kim PS: Formation of a Hydrophobic cluster in denatured bovine pancreatic trypsin inhibitor. J Mol Biol 1994, 236:412-420.
49. Pan H, Barbar E, Brany G, Woodward C: Extensive nonrandom structure in reduced and unfolded bovine pancreatic trypsin inhibitor. Biochemistry 1995, 34:13974-13981. This paper demonstrates that relatively small changes in conditions that lower the sample temperature can significantly change the amount of residual structure and/or its dynamics. Previous NMR studies of unfolded BPTI conducted at higher temperatures detected very little evidence of persistent structure.
50. Staley JP, Kim PS: Formation of a native-like subdomain in a partially folded intermediate of bovine pancreatic trypsin inhibitor. Protein Sci 1994, 3:1822-1832. A single disulfide bond (Cys30-Cys51) stabilizes approximately three quarters of the chain in a native-like subdomain, with the N-terminal 14 residues remaining as unfolded as in an isolated peptide. Together with the data reported in [50•], these results illustrate the extent to which parts of the BPTI domain can be uncoupled from one another.
51. Barbar E, Barany G, Woodward C: Dynamic structure of a highly ordered β-sheet molten globule: multiple conformations with a stable core. Biochemistry 1995, 34:11423-11434. A single disulfide bond (Cys14-Cys38) stabilizes approximately one quarter of the chain in a native-like domain which encompasses the hydrophobic core of the antiparallel β ribbon. Residues outside this core undergo relatively slow order-disorder transitions. Together with the data reported in [49•], these results illustrate the extent to which parts of the BPTI domain can be uncoupled from one another.
52. Logan TM, Theriault Y, Fesik SW: Structural characterization of the FK506 binding protein unfolded in urea and guanidine hydrochloride. J Mol Biol 1994, 236:637-648. A technical tour de force, in which nearly all of the side-chain and backbone resonances of a small protein are assigned in the urea-denatured state using a powerful new pulse sequence. Secondary shifts plus backbone NOEs are used to identify segments of residual structure, at least one of which has secondary structure different from that in the folded state.
53. Fan P, Bracken C, Baum J: Structural characterization of monellin in the alcohol-denatured state by NMR: evidence for β-sheet to α-helix conversion. Biochemistry 1993, 32:1573-1582.
54. Guijarro JI, Jackson M, Chaffotte AF, Delepierre M, Mantsch HH, Goldberg ME: Protein folding intermediates with rapidly exchangeable amide protons contain authentic hydrogen-bonded secondary structures. Biochemistry 1995, 34:2998-3008.
55. Liepinsh E, Otting G: Specificity of urea binding to proteins. J Am Chem Soc 1994, 116:9670-9674.
56. Blackledge MJ, Bruschweiler R, Griesinger C, Schmidt JM, Xu P, Ernest RR: Conformational backbone dynamics of the cyclic decapeptide antamanide. Application of a new conformational search algorithm based on NMR data. Biochemistry 1993, 32:10960-10974.
57. Kim Y, Prestegard JH: A dynamic model for the structure of acyl carrier protein in solution. Biochemistry 1989, 28:8792-8797.
58. Bonvin AMJJ, Brunger AT: Conformational variability of solution nuclear magnetic resonance structures. J Mol Biol 1995, 250:80-93. An important step toward using NMR data to recognize and characterize multiple conformations in a folded protein.