Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1998 Oct;7(10):2127–2135. doi: 10.1002/pro.5560071009

Effects of proline cis-trans isomerization on TB domain secondary structure.

X Yuan 1, J M Werner 1, V Knott 1, P A Handford 1, I D Campbell 1, K Downing 1
PMCID: PMC2143832  PMID: 9792099

Abstract

The transforming growth factor beta (TGF-beta) binding protein-like (TB) domain is found principally in proteins localized to extracellular matrix fibrils, including human fibrillin-1, the defective protein in the Marfan syndrome. Analysis of the nuclear magnetic resonance (NMR) data for the sixth TB module from human fibrillin-1 has revealed the existence of two stable conformers that differ in the isomerization states of two proline residues. Unusually, the two isoforms do not readily interconvert and are stable on the time scale of milliseconds. We have computed independent structures of the major and minor conformers of TB6 to assess how the domain fold adjusts to incorporate alternatively cis- or trans-prolines. Based on previous observations, it has been suggested that multiple conformers can only be accommodated in flexible regions of protein structure. In contrast, P22, which exists in trans in the major form and cis in the minor form of TB6, is in a rigid region of the domain, which is confirmed by backbone dynamics measurements. Overall, the structures of the major and minor conformers are similar. However, the secondary structure topologies of the two forms differ as a direct consequence of the changes in proline conformation.

Full Text

The Full Text of this article is available as a PDF (3.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adjadj E., Naudat V., Quiniou E., Wouters D., Sautière P., Craescu C. T. Solution structure of Lqh-8/6, a toxin-like peptide from a scorpion venom--structural heterogeneity induced by proline cis/trans isomerization. Eur J Biochem. 1997 May 15;246(1):218–227. doi: 10.1111/j.1432-1033.1997.00218.x. [DOI] [PubMed] [Google Scholar]
  2. Amodeo P., Morelli M. A., Castiglione Motta A. Multiple conformations and proline cis-trans isomerization in salmon calcitonin: a combined nuclear magnetic resonance, distance geometry, and molecular mechanics study. Biochemistry. 1994 Sep 6;33(35):10754–10762. doi: 10.1021/bi00201a024. [DOI] [PubMed] [Google Scholar]
  3. Chazin W. J., Kördel J., Drakenberg T., Thulin E., Brodin P., Grundström T., Forsén S. Proline isomerism leads to multiple folded conformations of calbindin D9k: direct evidence from two-dimensional 1H NMR spectroscopy. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2195–2198. doi: 10.1073/pnas.86.7.2195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chothia C., Finkelstein A. V. The classification and origins of protein folding patterns. Annu Rev Biochem. 1990;59:1007–1039. doi: 10.1146/annurev.bi.59.070190.005043. [DOI] [PubMed] [Google Scholar]
  5. Collod-Béroud G., Béroud C., Ades L., Black C., Boxer M., Brock D. J., Holman K. J., de Paepe A., Francke U., Grau U. Marfan Database (third edition): new mutations and new routines for the software. Nucleic Acids Res. 1998 Jan 1;26(1):229–223. doi: 10.1093/nar/26.1.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dallas S. L., Miyazono K., Skerry T. M., Mundy G. R., Bonewald L. F. Dual role for the latent transforming growth factor-beta binding protein in storage of latent TGF-beta in the extracellular matrix and as a structural matrix protein. J Cell Biol. 1995 Oct;131(2):539–549. doi: 10.1083/jcb.131.2.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans P. A., Dobson C. M., Kautz R. A., Hatfull G., Fox R. O. Proline isomerism in staphylococcal nuclease characterized by NMR and site-directed mutagenesis. Nature. 1987 Sep 17;329(6136):266–268. doi: 10.1038/329266a0. [DOI] [PubMed] [Google Scholar]
  8. Farrow N. A., Muhandiram R., Singer A. U., Pascal S. M., Kay C. M., Gish G., Shoelson S. E., Pawson T., Forman-Kay J. D., Kay L. E. Backbone dynamics of a free and phosphopeptide-complexed Src homology 2 domain studied by 15N NMR relaxation. Biochemistry. 1994 May 17;33(19):5984–6003. doi: 10.1021/bi00185a040. [DOI] [PubMed] [Google Scholar]
  9. Feng Y., Hood W. F., Forgey R. W., Abegg A. L., Caparon M. H., Thiele B. R., Leimgruber R. M., McWherter C. A. Multiple conformations of a human interleukin-3 variant. Protein Sci. 1997 Aug;6(8):1777–1782. doi: 10.1002/pro.5560060821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fox R. O., Evans P. A., Dobson C. M. Multiple conformations of a protein demonstrated by magnetization transfer NMR spectroscopy. Nature. 1986 Mar 13;320(6058):192–194. doi: 10.1038/320192a0. [DOI] [PubMed] [Google Scholar]
  11. Garcia de la Torre J. G., Bloomfield V. A. Hydrodynamic properties of complex, rigid, biological macromolecules: theory and applications. Q Rev Biophys. 1981 Feb;14(1):81–139. doi: 10.1017/s0033583500002080. [DOI] [PubMed] [Google Scholar]
  12. Garcia de la Torre J., Navarro S., Lopez Martinez M. C., Diaz F. G., Lopez Cascales J. J. HYDRO: a computer program for the prediction of hydrodynamic properties of macromolecules. Biophys J. 1994 Aug;67(2):530–531. doi: 10.1016/S0006-3495(94)80512-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gleizes P. E., Beavis R. C., Mazzieri R., Shen B., Rifkin D. B. Identification and characterization of an eight-cysteine repeat of the latent transforming growth factor-beta binding protein-1 that mediates bonding to the latent transforming growth factor-beta1. J Biol Chem. 1996 Nov 22;271(47):29891–29896. doi: 10.1074/jbc.271.47.29891. [DOI] [PubMed] [Google Scholar]
  14. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]
  15. Kay L. E., Torchia D. A., Bax A. Backbone dynamics of proteins as studied by 15N inverse detected heteronuclear NMR spectroscopy: application to staphylococcal nuclease. Biochemistry. 1989 Nov 14;28(23):8972–8979. doi: 10.1021/bi00449a003. [DOI] [PubMed] [Google Scholar]
  16. Kördel J., Forsén S., Drakenberg T., Chazin W. J. The rate and structural consequences of proline cis-trans isomerization in calbindin D9k: NMR studies of the minor (cis-Pro43) isoform and the Pro43Gly mutant. Biochemistry. 1990 May 8;29(18):4400–4409. doi: 10.1021/bi00470a020. [DOI] [PubMed] [Google Scholar]
  17. Laskowski R. A., Rullmannn J. A., MacArthur M. W., Kaptein R., Thornton J. M. AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR. 1996 Dec;8(4):477–486. doi: 10.1007/BF00228148. [DOI] [PubMed] [Google Scholar]
  18. Main A. L., Harvey T. S., Baron M., Boyd J., Campbell I. D. The three-dimensional structure of the tenth type III module of fibronectin: an insight into RGD-mediated interactions. Cell. 1992 Nov 13;71(4):671–678. doi: 10.1016/0092-8674(92)90600-h. [DOI] [PubMed] [Google Scholar]
  19. Murzin A. G., Brenner S. E., Hubbard T., Chothia C. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol. 1995 Apr 7;247(4):536–540. doi: 10.1006/jmbi.1995.0159. [DOI] [PubMed] [Google Scholar]
  20. Nilges M., Clore G. M., Gronenborn A. M. Determination of three-dimensional structures of proteins from interproton distance data by dynamical simulated annealing from a random array of atoms. Circumventing problems associated with folding. FEBS Lett. 1988 Oct 24;239(1):129–136. doi: 10.1016/0014-5793(88)80559-3. [DOI] [PubMed] [Google Scholar]
  21. Orengo C. A., Michie A. D., Jones S., Jones D. T., Swindells M. B., Thornton J. M. CATH--a hierarchic classification of protein domain structures. Structure. 1997 Aug 15;5(8):1093–1108. doi: 10.1016/s0969-2126(97)00260-8. [DOI] [PubMed] [Google Scholar]
  22. Saharinen J., Taipale J., Keski-Oja J. Association of the small latent transforming growth factor-beta with an eight cysteine repeat of its binding protein LTBP-1. EMBO J. 1996 Jan 15;15(2):245–253. [PMC free article] [PubMed] [Google Scholar]
  23. Sakai L. Y., Keene D. R., Glanville R. W., Bächinger H. P. Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. J Biol Chem. 1991 Aug 5;266(22):14763–14770. [PubMed] [Google Scholar]
  24. Scanlon M. J., Norton R. S. Multiple conformations of the sea anemone polypeptide anthopleurin-A in solution. Protein Sci. 1994 Jul;3(7):1121–1124. doi: 10.1002/pro.5560030717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Taipale J., Saharinen J., Hedman K., Keski-Oja J. Latent transforming growth factor-beta 1 and its binding protein are components of extracellular matrix microfibrils. J Histochem Cytochem. 1996 Aug;44(8):875–889. doi: 10.1177/44.8.8756760. [DOI] [PubMed] [Google Scholar]
  26. Yuan X., Downing A. K., Knott V., Handford P. A. Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils. EMBO J. 1997 Nov 17;16(22):6659–6666. doi: 10.1093/emboj/16.22.6659. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES