1932

Abstract

My research began with theory and methods for ultracentrifugal studies of proteins, first at the University of Wisconsin, Madison, with Bob Alberty and Jack Williams, then at Oxford University with A.G. (“Sandy”) Ogston, and finally back at Wisconsin with Williams and Lou Gosting. In 1959 I joined Arthur Kornberg's Biochemistry Department at Stanford University. Our first work was physical studies of DNA replication and then DNA physical chemistry, and DNA studies ended with the energetics of DNA twisting. In 1971 we began to search for protein folding intermediates by fast-reaction methods. We found the slow-folding and fast-folding forms of unfolded ribonuclease A, which led to the understanding that proline isomerization is sometimes part of the folding process. Using hydrogen exchange as a probe, we found the rapid formation of secondary structure during folding and used this to provide an NMR pulse labeling method for determining structures of folding intermediates. Our studies of peptide helices provided basic helix-coil parameters, also evidence for hierarchic folding, and further indicated that peptide hydrogen bonds are important in the energetics of folding.

Loading

Article metrics loading...

/content/journals/10.1146/annurev.biophys.37.032807.125948
2008-06-09
2024-06-20
Loading full text...

Full text loading...

/deliver/fulltext/bb/37/1/annurev.biophys.37.032807.125948.html?itemId=/content/journals/10.1146/annurev.biophys.37.032807.125948&mimeType=html&fmt=ahah

Literature Cited

  1. Avbelj F, Baldwin RL. 1.  2002. Role of backbone solvation in determining thermodynamic β-propensities of the amino acids. Proc. Natl. Acad. Sci. USA 99:1309–13 [Google Scholar]
  2. Avbelj F, Baldwin RL. 2.  2004. Origin of the neighboring residue effect on peptide backbone conformation. Proc. Natl. Acad. Sci. USA 101:10967–72 [Google Scholar]
  3. Avbelj F, Luo P, Baldwin RL. 3.  2000. Energetics of the interaction between water and the helical peptide group and its role in determining helix propensities. Proc. Natl. Acad. Sci. USA 97:10786–91 [Google Scholar]
  4. Baldwin RL. 4.  1953. Sedimentation coefficients of small molecules: methods of measurement based on the refractive-index gradient curve. The sedimentation coefficient of polyglucose A. Biochem. J. 55:644–48 [Google Scholar]
  5. Baldwin RL. 5.  1957. Boundary spreading in sedimentation velocity experiments. 4. Measurement of the standard deviation of a sedimentation coefficient distribution: application to bovine albumin and β-lactoglobulin. Biochem. J 65:490–502 [Google Scholar]
  6. Baldwin RL. 6.  1957. Boundary spreading in sedimentation velocity experiments. 5. Measurement of the diffusion coefficient of bovine albumin by Fujita's equation. Biochem. J. 65:503–12 [Google Scholar]
  7. Baldwin RL. 7.  1971. Experimental tests of the theory of deoxyribonucleic acid melting with d(T-A) oligomers. Acc. Chem. Res 4:265–72 [Google Scholar]
  8. Baldwin RL. 8.  1979. Discussions about proteins. In Origins of Molecular Biologyed. A Lwoff, A Ullmann pp. 203–207 New York: Academic [Google Scholar]
  9. Baldwin RL, Laughton PM, Alberty RA. 9.  1951. Homogeneity and the electrophoretic behavior of some proteins. III. A general method for the determination of mobility distributions. J. Phys. Colloid Chem. 55:111–25 [Google Scholar]
  10. Baldwin RL, Shooter EM. 10.  1963. The alkaline transition of BU-containing DNA and its bearing on the replication of DNA. J. Mol. Biol. 7:511–26 [Google Scholar]
  11. Barrick D, Baldwin RL. 11.  1993. Three-state analysis of sperm whale apomyoglobin folding. Biochemistry 32:3790–96 [Google Scholar]
  12. Bierzynski A, Kim PS, Baldwin RL. 12.  1982. A salt bridge stabilizes the helix formed by the isolated C-peptide of RNase A. Proc. Natl. Acad. Sci. USA 79:2470–74 [Google Scholar]
  13. Blum AD, Smallcombe SH, Baldwin RL. 13.  1978. Nuclear magnetic resonance evidence for a structural intermediate at an early stage in the refolding of ribonuclease A. J. Mol. Biol. 118:305–16 [Google Scholar]
  14. Brandts JF, Halvorson HR, Brennan M. 14.  1975. Consideration of the possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues. Biochemistry 14:4953–63 [Google Scholar]
  15. Brown JE, Klee WA. 15.  1971. Helix-coil transition of the isolated amino terminus of ribonuclease. Biochemistry 10:470–76 [Google Scholar]
  16. Cavalieri LF, Rosenberg BH, Deutsch JF. 16.  1959. The subunit of deoxyribonucleic acid. Biochem. Biophys. Res. Commun. 1:124–28 [Google Scholar]
  17. Chakrabartty A, Doig AJ, Baldwin RL. 17.  1993. Helix capping propensities in peptides parallel those in proteins. Proc. Natl. Acad. Sci. USA 90:11332–36 [Google Scholar]
  18. Chakrabartty A, Kortemme T, Baldwin RL. 18.  1994. Helix propensities of the amino acids measured in alanine-based peptides without helix-stabilizing side-chain interactions. Protein Sci. 3:843–52 [Google Scholar]
  19. Chakrabartty A, Schellman JA, Baldwin RL. 19.  1991. Large differences in the helix propensities of alanine and glycine. Nature 351:586–88 [Google Scholar]
  20. Cook KH, Schmid FX, Baldwin RL. 20.  1979. Role of proline isomerization in folding of ribonuclease A at low temperatures. Proc. Natl. Acad. Sci. USA 76:6157–61 [Google Scholar]
  21. Davies DR, Baldwin RL. 21.  1963. X-ray studies of two synthetic DNA copolymers. J. Mol. Biol. 6:251–55 [Google Scholar]
  22. Dill KA, Ozkan SB, Shell MS, Weikl TR. 22.  2008. The protein folding problem. Annu. Rev. Biophys. 37: In press [Google Scholar]
  23. Fujita H. 23.  1956. Effects of a concentration dependence of the sedimentation coefficient in velocity ultracentrifugation. J. Chem. Phys. 24:1084–90 [Google Scholar]
  24. Garel JR, Baldwin RL. 24.  1973. Both the fast and slow refolding reactions of ribonuclease A yield native enzyme. Proc. Natl. Acad. Sci. USA 70:3347–51 [Google Scholar]
  25. Garel JR, Nall BT, Baldwin RL. 25.  1976. Guanidine-unfolded state of ribonuclease A contains both fast- and slow-refolding species. Proc. Natl. Acad. Sci. USA 73:1853–57 [Google Scholar]
  26. Goch G, Maciejczyk M, Oleszczuk M, Stachowiak D, Malicka J, Bierzynski A. 26.  1993. Experimental investigation of initial steps of helix propagation in model peptides. Biochemistry 42:6840–47 [Google Scholar]
  27. Hagerman PJ, Baldwin RL. 27.  1976. A quantitative treatment of the folding transition of ribonuclease A. Biochemistry 15:1462–73 [Google Scholar]
  28. Hagerman PJ, Schmid FX, Baldwin RL. 28.  1979. Refolding behavior of a kinetic intermediate observed in low pH unfolding of ribonuclease A. Biochemistry 18:293–97 [Google Scholar]
  29. Hoeltzli S, Frieden C. 29.  1995. Stopped-flow NMR spectroscopy: real-time unfolding studies of 6–19F-tryptophan-labeled Escherichia coli dihydrofolate reductase. Proc. Natl. Acad. Sci. USA 92:9318–22 [Google Scholar]
  30. Houry WA, Rothwarf DM, Scheraga HA. 30.  1994. A very fast phase in the refolding of disulfide-intact ribonuclease A: implications for the refolding and unfolding pathway. Biochemistry 33:2516–30 [Google Scholar]
  31. Hughson FM, Barrick D, Baldwin RL. 31.  1991. Probing the stability of a partly folded apomyoglobin intermediate by site-directed mutagenesis. Biochemistry 30:4113–18 [Google Scholar]
  32. Hughson FM, Wright PE, Baldwin RL. 32.  1990. Structural characterization of a partly folded apomyoglobin intermediate. Science 249:1544–48 [Google Scholar]
  33. Huyghues-Despointes BMP, Klingler TM, Baldwin RL. 33.  1995. Measuring the strength of side-chain hydrogen bonds in peptide helices: the Gln·Asp (i,i+4) interaction. Biochemistry 34:13267–71 [Google Scholar]
  34. Huyghues-Despointes BMP, Scholtz JM, Baldwin RL. 34.  1993. Effect of a single aspartate on helix stability at different positions in a neutral alanine-based peptide. Protein Sci. 2:1604–11 [Google Scholar]
  35. Ihara S, Ooi T, Takahashi S. 35.  1982. Effects of salts on the nonequivalent stability of the α-helices of isomeric block copolypeptides. Biopolymers 21:131–45 [Google Scholar]
  36. Ikai A, Tanford C. 36.  1971. Kinetic evidence for incorrectly folded intermediate states in the refolding of denatured proteins. Nature 230:100–2 [Google Scholar]
  37. Inman RB, Baldwin RL. 37.  1962. Formation of hybrid molecules from two alternating DNA copolymers. J. Mol. Biol. 5:185–200 [Google Scholar]
  38. Inman RB, Baldwin RL. 38.  1962. Helix-random coil transitions in synthetic DNAs of alternating sequence. J. Mol. Biol. 5:172–84 [Google Scholar]
  39. Jamin M, Baldwin RL. 39.  1996. Refolding and unfolding kinetics of the equilibrium folding intermediate of apomyoglobin. Nat. Struct. Biol. 3:613–18 [Google Scholar]
  40. Jamin M, Baldwin RL. 40.  1998. Two forms of the pH 4 folding intermediate of apomyoglobin. J. Mol. Biol. 276:491–504 [Google Scholar]
  41. Karplus M, Weaver DL. 41.  1976. Protein-folding dynamics. Nature 260:404–6 [Google Scholar]
  42. Kay MS, Baldwin RL. 42.  1996. Packing interactions in the apomyoglobin folding intermediate. Nat. Struct. Biol. 3:439–45 [Google Scholar]
  43. Kiefhaber T, Baldwin RL. 43.  1995. Kinetics of hydrogen bond breakage in the process of unfolding of ribonuclease A measured by pulsed hydrogen exchange. Proc. Natl. Acad. Sci. USA 92:2657–61 [Google Scholar]
  44. Kiefhaber T, Labhardt AM, Baldwin RL. 44.  1995. Direct NMR evidence for an intermediate preceding the rate-limiting step in the unfolding of ribonuclease A. Nature 375:513–15 [Google Scholar]
  45. Kim PS, Baldwin RL. 45.  1984. A helix stop signal in the isolated S-peptide of ribonuclease A. Nature 307:329–34 [Google Scholar]
  46. Levinthal C. 46.  1968. Are there protein folding pathways?. J. Chim. Phys. 65:44–45 [Google Scholar]
  47. Levinthal C. 47.  1969. How to fold graciously. In Mössbauer Spectroscopy in Biological Systemsed. P Debrunner, JCM Tsibris, E Münck pp. 22–24 Urbana: Univ. Ill. Press [Google Scholar]
  48. Lifson S, Roig A. 48.  1961. On the theory of helix-coil transition in polypeptides. J. Chem. Phys. 34:517–28 [Google Scholar]
  49. Loh SN, Kay MS, Baldwin RL. 49.  1995. Structure and stability of a second molten globule intermediate in the apomyoglobin folding pathway. Proc. Natl. Acad. Sci. USA 92:5446–50 [Google Scholar]
  50. Lopez MM, Chin D-H, Baldwin RL, Makhatadze GI. 50.  2002. The enthalpy of the alanine peptide helix measured by isothermal titration calorimetry using metal-binding to induce helix formation. Proc. Natl. Acad. Sci. USA 99:1298–302 [Google Scholar]
  51. Lotan N, Yaron A, Berger A. 51.  1966. The stabilization of the α-helix in aqueous solution by hydrophobic side-chain interaction. Biopolymers 4:365–68 [Google Scholar]
  52. Luo P, Baldwin RL. 52.  1999. Interaction between water and polar groups of the helix backbone: an important determinant of helix propensities. Proc. Natl. Acad. Sci. USA 96:4930–35 [Google Scholar]
  53. Luo Y, Kay MS, Baldwin RL. 53.  1997. Cooperativity of folding of the apomyoglobin pH 4 folding intermediate studied by glycine and proline mutations. Nat. Struct. Biol. 4:925–30 [Google Scholar]
  54. Marqusee S, Robbins VH, Baldwin RL. 54.  1989. Unusually stable helix formation in alanine-based peptides. Proc. Natl. Acad. Sci. USA 86:5286–90 [Google Scholar]
  55. Meselson M, Stahl FW. 55.  1958. The replication of DNA in Escherichia coli. Proc. Natl. Acad. Sci. USA 44:671–82 [Google Scholar]
  56. Monod J, Wyman J, Changeux J-P. 56.  1965. On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12:88–118 [Google Scholar]
  57. Nall BT, Garel J-R, Baldwin RL. 57.  1978. Test of the extended two-state model for the kinetic intermediates observed in the folding transition of ribonuclease A. J. Mol. Biol. 118:317–30 [Google Scholar]
  58. Oncley JL. 58. ed. 1959. Biophysical Science—A Study Program New York: Wiley [Google Scholar]
  59. Padmanabhan S, Baldwin RL. 59.  1994. Tests for helix-stabilizing interactions between various nonpolar side-chains in alanine-based peptides. Protein Sci. 3:1992–97 [Google Scholar]
  60. Padmanabhan S, York EJ, Gera L, Stewart JM, Baldwin RL. 60.  1994. Helix-forming tendencies of amino acids in short (hydroxybutyl)-L-glutamine peptides: an evaluation of the contradictory results from host-guest studies and short alanine-based peptides. Biochemistry 33:8604–9 [Google Scholar]
  61. Pohl FM. 61.  1969. On the kinetics of structural transition I of some pancreatic proteins. FEBS Lett. 3:60–64 [Google Scholar]
  62. Ptitsyn OB. 62.  1973. The stepwise mechanism of protein self-organization. Dokl. Nauk. SSSR 210:1213–15 [Google Scholar]
  63. Rice SA, Doty P. 63.  1957. The thermal denaturation of deoxyribose nucleic acid. J. Am. Chem. Soc. 79:3937–47 [Google Scholar]
  64. Robertson AD, Purisima EO, Eastman MA, Scheraga HA. 64.  1989. Proton NMR assignments and regular backbone structure of bovine pancreatic ribonuclease A in aqueous solution. Biochemistry 28:5930–38 [Google Scholar]
  65. Roder H, Elöve G, Englander SW. 65.  1988. Structural characterization of folding intermediates in cytochrome c by H-exchange labelling and proton NMR. Nature 335:700–4 [Google Scholar]
  66. Roder H, Wüthrich K. 66.  1986. Protein folding kinetics by combined use of rapid mixing techniques and NMR observation of individual amide protons. Proteins Struct. Funct. Genet. 1:34–42 [Google Scholar]
  67. Rohl CA, Chakrabartty A, Baldwin RL. 67.  1996. Helix propagation and N-cap propensities of the amino acids measured in alanine-based peptides in 40 volume percent trifluoroethanol. Protein Sci. 5:2623–37 [Google Scholar]
  68. Rohl CA, Scholtz JM, York EJ, Stewart JM, Baldwin RL. 68.  1992. Kinetics of amide proton exchange in helical peptides of varying chain lengths. Interpretation by the Lifson-Roig theory. Biochemistry 31:1263–69 [Google Scholar]
  69. Rose GD. 69.  1979. Hierarchic organization of domains in globular proteins. J. Mol. Biol. 134:447–70 [Google Scholar]
  70. Scheffler IE, Elson EL, Baldwin RL. 70.  1968. Helix formation by dAT oligomers. I. Hairpin and straight-chain helices. J. Mol. Biol. 36:291–304 [Google Scholar]
  71. Scheffler IE, Elson EL, Baldwin RL. 71.  1970. Helix formation by d(TA) oligomers. II. Analysis of the helix-coil transitions of linear and circular oligomers. J. Mol. Biol. 48:145–71 [Google Scholar]
  72. Schmid FX, Baldwin RL. 72.  1978. Acid catalysis of the formation of the slow-folding species of ribonuclease A: evidence that the reaction is proline isomerization. Proc. Natl. Acad. Sci. USA 75:4764–68 [Google Scholar]
  73. Schmid FX, Baldwin RL. 73.  1979. Detection of an early intermediate in the folding of ribonuclease A by protection of amide protons against exchange. J. Mol. Biol. 135:199–215 [Google Scholar]
  74. Scholtz JM, Qian H, York EJ, Stewart JM, Baldwin RL. 74.  1991. Parameters of helix-coil transition theory for alanine-based peptides of varying chain lengths in water. Biopolymers 31:1463–70 [Google Scholar]
  75. Scholtz JM, York EJ, Stewart JM, Baldwin RL. 75.  1991. A neutral, water-soluble, α-helical peptide: the effect of ionic strength on the helix-coil equilibrium. J. Am. Chem. Soc. 113:5102–4 [Google Scholar]
  76. Shoemaker KR, Fairman R, Kim PS, York EJ, Stewart JM, Baldwin RL. 76.  1987. The C-peptide helix from ribonuclease A considered as an autonomous folding unit. Cold Spring Harbor Symp. Quant. Biol. LII:391–98 [Google Scholar]
  77. Shoemaker KR, Kim PS, York EJ, Stewart JM, Baldwin RL. 77.  1987. Tests of the helix dipole model for the stabilization of α-helices. Nature 326:563–67 [Google Scholar]
  78. Shore D, Baldwin RL. 78.  1983. Energetics of DNA twisting. I. Relation between twist and cyclization probability. J. Mol. Biol. 170:957–81 [Google Scholar]
  79. Takahashi S, Kim E-H, Hibino T, Ooi T. 79.  1989. Comparison of alpha-helix stability in peptides having a negatively or positively charged residue block attached either to the N- or C-terminus of an alpha-helix. The electrostatic contribution and anisotropic stability of the alpha-helix. Biopolymers 28:995–1009 [Google Scholar]
  80. Tsong TY, Baldwin RL. 80.  1972. Kinetic evidence for intermediate states in the unfolding of chymotrypsinogen A. J. Mol. Biol. 69:145–48 [Google Scholar]
  81. Tsong TY, Baldwin RL, Elson EL. 81.  1971. The sequential unfolding of ribonuclease A: detection of a fast initial phase in the kinetics of unfolding. Proc. Natl. Acad. Sci. USA 68:2712–15 [Google Scholar]
  82. Udgaonkar J. 82.  2008. Multiple routes and structural heterogeneity in protein folding. Annu. Rev. Biophys 37:489–510 [Google Scholar]
  83. Udgaonkar JB, Baldwin RL. 83.  1988. NMR evidence for an early framework intermediate on the folding pathway of ribonuclease A. Nature 335:694–99 [Google Scholar]
  84. Van Holde KE, Baldwin RL. 84.  1958. Rapid attainment of sedimentation equilibrium. J. Phys. Chem. 62:734–43 [Google Scholar]
  85. Wake RG, Baldwin RL. 85.  1962. Physical studies on the replication of DNA in vitro. J. Mol. Biol. 5:201–16 [Google Scholar]
  86. Zimm BH, Bragg JK. 86.  1959. Theory of the phase transition between helix and random coil in polypeptide chains. J. Chem. Phys. 31:476–85 [Google Scholar]
/content/journals/10.1146/annurev.biophys.37.032807.125948
Loading
  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error