Abstract
THE potential use of monoclonal antibodies in immunological, chemical and clinical applications has stimulated the protein engineering and expression of Fv fragments1–8, which are heterodimers consisting of the light and heavy chain variable domains (VL and VH) of antibodies. Although Fv fragments exhibit antigen binding specificity and association constants similar to their parent antibodies or Fab moieties, similarity in their interactions with antigen at the level of three-dimensional structure has not been investigated. We have determined the high-resolution crystal structure of the genetically engineered FvD1.3 fragment1 of the anti-hen egg-white lysozyme (HEL) monoclonal antibody D1.3 (ref. 9), and of its complex with HEL. On comparison with the crystallographically refined FabD1.3-HEL complex, we find that FvD1.3 and FabD1.3 make, with minor exceptions, very similar contacts with the antigen. Furthermore, a small but systematic rearrangement of the domains of FvD1.3 occurs on binding HEL, bringing the contacting residues closer to the antigen by a mean value of about 0.7 Å for VH (aligning on VL) or of 0.5 Å for VL (aligning on VH). This is indicative of an induced fit rather than a 'lock and key' fit to the antigen.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ward, E. S., Güssow, D., Griffiths, A. O., Jones, P. T. & Winter, G. Nature 341, 544–546 (1989).
Better, M., Chang, C. P., Robinson, R. R. & Hurwitz, A. H. Science 240, 1041–1043 (1988).
Huston, J. S. et al. Proc. natn. Acad. Sci. U.S.A. 85, 5879–5883 (1988).
Bird, R. E. et al. Science 242, 423–426 (1988).
Chaudhary, V. K. et al. Nature 339, 394–397 (1989).
Glockshuber, R., Malia, M., Pfitzinger, I. & Plückthun, A. Biochemistry 29, 1362–1367 (1990).
Sastry, L. et al. Proc. natn. Acad. Sci. U.S.A. 86, 5728–5732 (1989).
Udata, K. et al. Molec. Immun. 27, 25–35 (1990).
Harper, M., Lema, F., Boulot, G. & Poljak, R. J. molec. Immun. 24, 97–108 (1987).
Boulot, G. et al. J. molec. Biol. 213, 617–619 (1990).
Mariuzza, R. A. et al. J. molec. Biol. 170, 1055–1058 (1983).
Amit, A. G., Mariuzza, R. A., Phillips, S. E. V. & Poljak, R. J. Science 233, 747–753 (1986).
Brünger, A., Kurian, J. & Karplus, M. Science 235, 458–460 (1987).
Luzzati, V. Acta crystallogr. 5, 802–810 (1952).
Colman, P. M. et al. Nature 326, 358–363 (1987).
Stevens, F. J., Chang, C. H. & Schiffer, M. Proc. natn. Acad. Sci. U.S.A. 85, 6895–6899 (1988).
Lascombe, M. B. et al. Proc. natn. Acad. Sci. U.S.A. 86, 607–611 (1989).
Davies, D. R., Sheriff, S. & Padlan, E. A. J. biol. Chem. 263, 10541–10544 (1988).
Levitt, M. & Perutz, M. F. J. molec. Biol. 201, 751–754 (1988).
Kabsch, W. J. appl. Crystallogr. 21, 916–924 (1988).
Jones, A. J. appl. Crystallogr. 11, 268–272 (1978).
Pflugrath, J. W., Saper, M. A. & Quiocho, F. A. in Methods and Applications of Crystallographic Computing (eds Hall, S. & Ashiaka, I.) 404–407 (Clarendon, Oxford, 1984).
Sheriff, S., Hendrickson, W. A. & Smith, J. L. J. molec. Biol. 197, 273–296 (1987).
Tulip, W. et al. Cold Spring Harbor Symp. quant. biol. 54, 257–263 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bhat, T., Bentley, G., Fischmann, T. et al. Small rearrangements in structures of Fv and Fab fragments of antibody D 1.3 on antigen binding. Nature 347, 483–485 (1990). https://doi.org/10.1038/347483a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/347483a0
This article is cited by
-
Peptide-Conjugation Induced Conformational Changes in Human IgG1 Observed by Optimized Negative-Staining and Individual-Particle Electron Tomography
Scientific Reports (2013)
-
Polyreactive antibodies in adaptive immune responses to viruses
Cellular and Molecular Life Sciences (2012)
-
Interactions between anti-ErbB2 antibody A21 and the ErbB2 extracellular domain provide a basis for improving A21 affinity
Journal of Computer-Aided Molecular Design (2010)
-
Predicting the distance between antibody’s interface residue and antigen to recognize antigen types by support vector machine
Neural Computing and Applications (2007)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.