Abstract
Protein hydrogen exchange is generally believed to register some aspects of internal protein dynamics, but the kind of motion at work is not clear. Experiments are being done to identify the determinants of protein hydrogen exchange and to distinguish between local unfolding and accessibility-penetration mechanisms. Results with small molecules, polynucleotides, and proteins demonstrate that solvent accessibility is by no means sufficient for fast exchange. H-exchange slowing is quite generally connected with intramolecular H-bonding, and the exchange process depends pivotally on transient H-bond cleavage. At least in alpha-helical structures, the cooperative aspect of H-bond cleavage must be expressed in local unfolding reactions. Results obtained by use of a difference hydrogen exchange method appear to provide a direct measurement of transient, cooperative, local unfolding reactions in hemoglobin. The reality of these supposed coherent breathing units is being tested by using the difference H-exchange approach to tritium label the units one at a time and then attempting to locate the tritium by fragmenting the protein, separating the fragments, and testing them for label. Early results demonstrate the feasibility of this approach.
Full text
PDF










Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ellis L. M., Bloomfield V. A., Woodward C. K. Hydrogen-tritium exchange kinetics of soybean trypsin inhibitor (Kunitz). Solvent accessibility in the folded conformation. Biochemistry. 1975 Jul 29;14(15):3413–3419. doi: 10.1021/bi00686a019. [DOI] [PubMed] [Google Scholar]
- Englander J. J., Kallenbach N. R., Englander S. W. Hydrogen exchange study of some polynucleotides and transfer RNA. J Mol Biol. 1972 Jan 14;63(1):153–169. doi: 10.1016/0022-2836(72)90527-x. [DOI] [PubMed] [Google Scholar]
- Englander S. W., Downer N. W., Teitelbaum H. Hydrogen exchange. Annu Rev Biochem. 1972;41:903–924. doi: 10.1146/annurev.bi.41.070172.004351. [DOI] [PubMed] [Google Scholar]
- Englander S. W., Englander J. J. Hydrogen--tritium exchange. Methods Enzymol. 1978;49:24–39. doi: 10.1016/s0076-6879(78)49005-6. [DOI] [PubMed] [Google Scholar]
- Englander S. W., Mauel C. Hydrogen exchnge studies of respiratory proteins. II. Detection of discrete, ligand-induced changes in hemoglobin. J Biol Chem. 1972 Apr 25;247(8):2387–2394. [PubMed] [Google Scholar]
- Englander S. W. Measurement of structural and free energy changes in hemoglobin by hydrogen exchange methods. Ann N Y Acad Sci. 1975 Apr 15;244:10–27. doi: 10.1111/j.1749-6632.1975.tb41518.x. [DOI] [PubMed] [Google Scholar]
- Englander S. W., Rolfe A. Hydrogen exchange studies of respiratory proteins. 3. Structural and free energy changes in hemoglobin by use of a difference method. J Biol Chem. 1973 Jul 10;248(13):4852–4861. [PubMed] [Google Scholar]
- Ghose R. C., Englander S. W. Hydrogen exchange studies of respiratory proteins. IV. A new, ligand-responsive class in hemoglobin. J Biol Chem. 1974 Dec 25;249(24):7950–7955. [PubMed] [Google Scholar]
- Hilton B. D., Woodward C. K. Nuclear magnetic resonance measurement of hydrogen exchange kinetics of single protons in basic pancreatic trypsin inhibitor. Biochemistry. 1978 Aug 8;17(16):3325–3332. doi: 10.1021/bi00609a024. [DOI] [PubMed] [Google Scholar]
- Hvidt A., Nielsen S. O. Hydrogen exchange in proteins. Adv Protein Chem. 1966;21:287–386. doi: 10.1016/s0065-3233(08)60129-1. [DOI] [PubMed] [Google Scholar]
- Lakowicz J. R., Weber G. Quenching of protein fluorescence by oxygen. Detection of structural fluctuations in proteins on the nanosecond time scale. Biochemistry. 1973 Oct 9;12(21):4171–4179. doi: 10.1021/bi00745a021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mandal C., Kallenbach N. R., Englander S. W. Base-pair opening and closing reactions in the double helix. A stopped-flow hydrogen exchange study in poly(rA).poly(rU). J Mol Biol. 1979 Dec 5;135(2):391–411. doi: 10.1016/0022-2836(79)90443-1. [DOI] [PubMed] [Google Scholar]
- McCammon J. A., Gelin B. R., Karplus M. Dynamics of folded proteins. Nature. 1977 Jun 16;267(5612):585–590. doi: 10.1038/267585a0. [DOI] [PubMed] [Google Scholar]
- Molday R. S., Englander S. W., Kallen R. G. Primary structure effects on peptide group hydrogen exchange. Biochemistry. 1972 Jan 18;11(2):150–158. doi: 10.1021/bi00752a003. [DOI] [PubMed] [Google Scholar]
- Perutz M. F. Stereochemistry of cooperative effects in haemoglobin. Nature. 1970 Nov 21;228(5273):726–739. doi: 10.1038/228726a0. [DOI] [PubMed] [Google Scholar]
- Rosa J. J., Richards F. M. An experimental procedure for increasing the structural resolution of chemical hydrogen-exchange measurements on proteins: application to ribonuclease S peptide. J Mol Biol. 1979 Sep 25;133(3):399–416. doi: 10.1016/0022-2836(79)90400-5. [DOI] [PubMed] [Google Scholar]
- SCHELLMAN J. A. The stability of hydrogen-bonded peptide structures in aqueous solution. C R Trav Lab Carlsberg Chim. 1955;29(14-15):230–259. [PubMed] [Google Scholar]
- Teitelbaum H., Englander S. W. Open states in native polynucleotides. II. Hydrogen-exchange study of cytosine-containing double helices. J Mol Biol. 1975 Feb 15;92(1):79–92. doi: 10.1016/0022-2836(75)90092-3. [DOI] [PubMed] [Google Scholar]
- Wagner G., Wüthrich K. Structural interpretation of the amide proton exchange in the basic pancreatic trypsin inhibitor and related proteins. J Mol Biol. 1979 Oct 15;134(1):75–94. doi: 10.1016/0022-2836(79)90414-5. [DOI] [PubMed] [Google Scholar]
- Woodward C. K., Hilton B. D. Hydrogen exchange kinetics and internal motions in proteins and nucleic acids. Annu Rev Biophys Bioeng. 1979;8:99–127. doi: 10.1146/annurev.bb.08.060179.000531. [DOI] [PubMed] [Google Scholar]
- Yee R. Y., Englander S. W., Von Hippel P. H. Native collagen has a two-bonded structure. J Mol Biol. 1974 Feb 15;83(1):1–16. doi: 10.1016/0022-2836(74)90420-3. [DOI] [PubMed] [Google Scholar]