The nature of antibody heavy chain residue H6 strongly influences the stability of a V(H) domain lacking the disulfide bridge

Journal of Molecular Biology

Volumn 283, Issue 1, 1998, Pages 95-110

  Langedijk, Annette C ^a,b   Honegger, Annemarie ^a   Maat, Jan ^c   Planta, Rudi J ^b   Van Schaik, René C ^c,d   Plückthun, Andreas ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b VU UNIVERSITY AMSTERDAM   (Netherlands)

^c UNILEVER RESEARCH VLAARDINGEN   (Netherlands)

^d Agro Business Park 90   (Netherlands)

Author keywords

Antibody engineering; Disulfide bond; Intrabodies; Protein folding; scFv fragment

Indexed keywords

CYSTEINE; GLUTAMIC ACID; GLUTAMINE; IMMUNOGLOBULIN HEAVY CHAIN; MONOCLONAL ANTIBODY; RECOMBINANT PROTEIN; SERINE;

ARTICLE; DISULFIDE BOND; HYDROGEN BOND; IMMUNOGLOBULIN VARIABLE REGION; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN STABILITY; SOMATIC MUTATION;

EID: 0032538296     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1006/jmbi.1998.2064     Document Type: Article

References (42)

1. Anderson, G. W., Zimmerman, J. E. & Callahan, F. M. (1964). The use of esters of N-hydroxysuccinimide in peptide synthesis. J. Am. Chem. Soc. 86, 1839-1842.
2. Benhar, I. & Pastan, I. (1995). Identification of residues that stabilize the single-chain Fv of monoclonal antibody B3. J. Biol. Chem. 270, 23373-23380.
3. Brewer, J. M., Pesce, A. J. & Anderson, R. B. (1974). Absorption and fluorescence. In Experimental Techniques in Biochemistry (Hager, L. & Wold, F., eds), pp. 216-262, Prentice-Hall, New Jersey.
4. Buchner, J. & Rudolph, R. (1991). Renaturation, purification and characterization of recombinant Fabfragments produced in Escherichia coli. Biotechnology, 9,157-162.
5. Chan, W., Helms, L. R., Brooks, I., Lee, G., Ngola, S., McNulty, D., Maleeff, B., Hensley, P. & Wetzel, R. (1996). Mutational effects on inclusion body formation in the periplasmic expression of the immunoglobulin VL domain REI. Folding Des. 1, 77-89.
6. Chitarra, V., Alzari, P. M., Bentley, G. A., Bhat, T. N., Eisele, J. L., Houdusse, A., Lescar, J., Souchon, H. & Poljak, R. J. (1993). Three-dimensional structure of a heteroclitic antigen-antibody cross-reaction complex. Proc. Natl Acad. Sci. USA, 90, 7711-7715.
7. Chomczynski, P. & Sacchi, N. (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156-159.
8. Cowgill, R. W. (1967). Fluorescence and protein structure. XI. Fluorescence quenching by disulfide and sulfhydryl groups. Biochim. Biophys. Acta, 140, 37-43.
9. Cuisinier, A. M., Gauthier, L., Boubli, L., Fougereau, M. & Tonnelle, C. (1993). Mechanisms that generate human immunoglobulin diversity operate from the 8th week of gestation in fetal liver. Eur. J. Immunol, 23, 110-118.
10. Dao-pin, S., Anderson, D. E., Baase, W. A., Dahlquist, F. W. & Matthews, B. W. (1991). Structural an thermodynamic consequences of burying a charged residue within the hydrophobic core of T4 lysozyme. Biochemistry, 30, 11521-11529.
11. K on the reactivity of scFv-s. Hum. Antibodies Hybridomas, 6, 36.
12. Freund, C., Ross, A., Guth, B., Plückthun, A. & Holak, T. A. (1993). Characterization of the linker peptide of the single-chain Fv fragment of an antibody by NMR spectroscopy. FEBS Letters, 320, 97-100.
13. v, the variable domain of a human immunoglobulin kappa light chain. Folding Des. 1, 431-440.
14. Gargano, N. & Cattaneo, A. (1997). Rescue of a neutralizing anti-viral antibody fragment from an intracellular polyclonal repertoire expressed in mammalian cells. FEBS Letters, 414, 537-540.
15. Ge, L., Knappik, A., Pack, P., Freund, C. & Plückthun, A. (1995). Expressing antibodies in Escherichia coli. In Antibody Engineering (Borrebaeck, C. A. K., ed.), 2nd edit., pp. 229-266, Oxford University Press.
16. Gill, S. C. & von Hippel, P. H. (1989). Calculation of protein extinction coefficients from amino acid sequence data. Anal. Biochem. 182, 319-326.
17. Glockshuber, R., Schmidt, T. & Plückthun, A. (1992). The disulfide bonds in antibody variable domains: effects on stability, folding in vitro, and functional expression in Escherichia coli. Biochemistry, 31, 1270-1279.
18. Jannot, C. B., Beerli, R. R., Mason, S., Gullick, W. J. & Hynes, N E. (1996). Intracellular expression of a single-chain antibody directed to the EGFR leads to growth inhibition of tumor cells. Oncogene, 13, 275-282.
19. Jung, S. & Plückthun, A. (1997). Improving in vivo folding and stability of a single-chain Fv antibody fragment by loop grafting. Protein Eng. 10, 959-966.
20. Kabat, E. A., Wu, T. T., Perry, H. M., Gottesman, K. S. & Foeller, C. (1991). Sequences of Proteins of Immunological Interest, 5th edit., U.S. Department of Health and Human Services, Public Health Service National Institutes of Health, Bethesda, MD.
21. Kipriyanov, S. M., Moldenhauer, G., Martin, A. C. R., Kupriyanova, O. A. & Little, M. (1997). Two amino acid mutations in an anti-human CD3 single-chain Fv antibody fragment that affect the yield on bacterial secretion but not the affinity. Protein Eng. 10, 445-453.
22. Knappik, A. & Plückthun, A. (1994). An improved affinity tag based on the FLAG® peptide for the detection and purification of recombinant antibody fragments. Biotechniques, 17, 754-761.
23. Langsetmo, K., Fuchs, J. A., Woodward, C. & Sharp, K. A. (1991). Linkage of thioredoxin stability to titration of ionizable groups with perturbed pKa. Biochemistry, 30, 7609-7614.
24. Liu, Y., Breslauer, K. & Anderson, S. (1997). "Designing out" disulfide bonds: thermodynamic properties of 30-51 cysteine substitution mutants of bovine pancreatic trypsin inhibitor. Biochemistry, 36, 5323-5335.
25. 2 made by protein folding and bonded through C-terminal cysteinyl peptides. Protein Eng. 8, 301-314.
26. Mitamura, K., Suenaga, R., Wilson, K. B. & Abdou, N. I. (1996). V Gene sequences of human anti-ssDNA antibodies secreted by lupus-derived CD5-negative B cell hybridomas. Clin. Immunol. Immunopathol. 78, 152-160.
27. Pace, C. N. & Scholtz, J. M. (1997). Measuring the conformational stability of a protein. In Protein Structure: A Practical Approach (Creighton, T. E., ed.), pp. 299-321, IRL Press, Oxford.
28. Persic, L., Righi, M., Roberts, A., Hoogenboom, H. R., Cattaneo, A. & Bradbury, A. (1997). Targeting vectors for intracellular immunisation. Gene, 187, 1-8.
29. Podell, D. N. & Abraham, G. N. (1978). A technique for the removal of pyroglutamic acid from the amino terminus of proteins using calf liver pyroglutamate amino peptidase. Biochem. Biophys. Res. Commun. 81, 176-185.
30. H: consequences for thermodynamic stability and folding. J. Mol. Biol. 265, 161-172.
31. Proba, K., Wörn, A., Honegger, A. & Plückthun, A. (1998). Antibody scFv fragments without disulfide bonds made by molecular evolution. J. Mol. Biol. 275, 245-253.
32. Riddles, P., Blakeley, R. L. & Zerner, B. (1983). Reassessment of Ellmans's reagent. Methods Enzymol. 91, 49-60.
33. Rudikoff, S. & Pumphrey, J. G. (1986). Functional antibody lacking a variable-region disulfide bridge. Proc. Natl Acad. Sci. USA, 83, 7875-7878.
34. Spada, S., Honegger, A. & Plückthun, A. (1998). Reproducing the natural evolution of protein structural features with the selectively infective phage (SIP) technology: The kink in the first strand of antibody kappa domains. J. Mol. Biol. In the press.
35. Studier, F. W. & Moffatt, B. A. (1986). Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J. Mol. Biol. 189, 113-130.
36. Tissot, A. C., Vuilleumier, S. & Fersht, A. R. (1996). Importance of two buried salt bridges in the stability and folding pathway of barnase. Biochemistry, 35, 6786-6794.
37. Tsunenaga, M., Goto, Y., Kawata, Y. & Hamaguchi, K. (1987). Unfolding and refolding of a type kappa immunoglobulin light chain and its variable and constant fragments. Biochemistry, 26, 6044-6051.
38. Whitlow, M., Howard, A. J., Wood, J. F., Voss, E. W., Jr. & Hardman, K. D. (1995). 1.85 Å structure of antifluorescein 4-4-20 Fab. Protein Eng. 8, 749-761.
39. Wörn, A. & Plückthun, A. (1998a). An intrinsically stable antibody scFv fragment can tolerate the loss of both disulfide bonds and fold correctly. FEBS Letters, 427, 357-351.
40. H in single-chain antibody fragments, investigated with mutants engineered for stability. Biochemistry, In the press.
41. Yang, X., Stedra, J. & Cerny, J. (1996). Relative contribution of T and B cells to hypermutation and selection of the antibody repertoire in germinal centers of aged mice. J. Exp. Med. 183, 959-970.
42. Yanisch-Perron, C., Vieira, J. & Messing, J. (1985). Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene, 33, 103-119.