Abstract
Recent advances in the sequencing of whole genomes have given fascinating insights into the overall composition of the encoded proteins. Many of the amino acid sequences that have been deduced in this way have highly biased sequences and are predicted to be unfolded. A significant number of these sequences correspond to parts of functional proteins, and in a surprising number of cases, the unstructured regions correspond to the most relevant parts of the protein for function – the actual sites for the binding of activators, repressors, and other ligands. This is particularly true for proteins involved in signaling networks – that is, signal transduction, transcriptional activation, translation, and cell cycle regulation. The intrinsically disordered regions facilitate interactions with multiple binding partners and also provide a means for efficiently dissociating the complex after the signal has been transduced. This article briefly reviews some of the recent experimental evidence from our own and other labs, upon which these conclusions are based.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
P.E. Wright, H.J. Dyson, J. Mol. Biol. 293, 321 (1999)
V.N. Uversky, Protein Sci. 11, 739 (2002)
A.K. Dunker, C.J. Brown, Adv. Protein Chem. 62, 25 (2002)
P. Tompa, Trends Biochem. Sci. 27, 527 (2002)
H.J. Dyson, P.E. Wright, Nat. Rev. Mol. Cell Biol. 6, 197 (2005)
R.B. Russell, T.J. Gibson, FEBS Lett. 582, 1271 (2008)
C. Bösch, A. Bundi, M. Oppliger, K. Wüthrich, Eur. J. Biochem. 91, 209 (1978)
X. He, D. Chow, M.M. Martick, K.C. Garcia, Science 293, 1657 (2001)
A.J. Daniels, R.J.P. Williams, P.E. Wright, Neuroscience 3, 573 (1978)
R.W. Kriwacki, L. Hengst, L. Tennant, S.I. Reed, P.E. Wright, Proc. Natl. Acad. Sci. USA 93, 11504 (1996)
G.W. Daughdrill, M.S. Chadsey, J.E. Karlinsey, K.T. Hughes, F.W. Dahlquist, Nat. Struct. Biol. 4, 285 (1997)
G.W. Daughdrill, L.J. Hanely, F.W. Dahlquist, Biochemistry 37, 1076 (1998)
I. Radhakrishnan, G.C. Pérez-Alvarado, D. Parker, H.J. Dyson, M.R. Montminy, P. E. Wright, Cell 91, 741 (1997)
I. Radhakrishnan, G.C. Pérez-Alvarado, H.J. Dyson, P.E. Wright, FEBS Lett. 430, 317 (1998)
D. Liu, R. Ishima, K.I. Tong, S. Bagby, T. Kokubo, D.R. Muhandiram, L.E. Kay, Y. Nakatani, M. Ikura, Cell 94, 573 (1998)
P. Romero, Z. Obradovic, C.R. Kissinger, J.E. Villafranca, E. Garner, S. Guilliot, A.K. Dunker, Pac. Symp. Biocomput. 3, 437 (1998)
P. Romero, Z. Obradovic, C.R. Kissinger, J.E. Villafranca, A.K. Dunker, Proc. IEEE Int. Conf. Neural Networks 1997, 90 (1997)
L.M. Iakoucheva, C.J. Brown, J.D. Lawson, Z. Obradovic, A.K. Dunker, J. Mol. Biol. 323, 573 (2002)
N. Abdul-Manan, B. Aghazadeh, G.A. Liu, A. Majumdar, O. Ouerfelli, K.A. Siminovitch, M.K. Rosen, Nature 399, 379 (1999)
A.H. Huber, D.B. Stewart, D.V. Laurents, W.J. Nelson, W.I. Weis, J. Biol. Chem. 276, 12301 (2001)
S.A. Dames, M. Martinez-Yamout, R.N. De Guzman, H.J. Dyson, P.E. Wright, Proc. Natl. Acad. Sci. USA 99, 5271 (2002)
R.N. De Guzman, M. Martinez-Yamout, H.J. Dyson, P.E. Wright, J. Biol. Chem. 279, 3042 (2004)
S.J. Demarest, M. Martinez-Yamout, J. Chung, H. Chen, W. Xu, H.J. Dyson, R.M. Evans, P.E. Wright, Nature 415, 549 (2002)
N.K. Goto, T. Zor, M. Martinez-Yamout, H.J. Dyson, P.E. Wright, J. Biol. Chem. 277, 43168 (2002)
P.E. Hershey, S.M. McWhirter, J.D. Gross, G. Wagner, T. Alber, A.B. Sachs, J. Biol. Chem. 274, 21297 (1999)
H.J. Dyson, P.E. Wright, Curr. Opin. Struct. Biol. 12, 54 (2002)
J. Yao, H.J. Dyson, P.E. Wright, FEBS Lett. 419, 285 (1997)
K. Sugase, H.J. Dyson, P.E. Wright, Nature 447, 1021 (2007)
K. Gunasekaran, C.J. Tsai, S. Kumar, D. Zanuy, R. Nussinov, Trends Biochem. Sci. 28, 81 (2003)
J.M. Elkins, K.S. Hewitson, L.A. McNeill, J.F. Seibel, I. Schlemminger, C.W. Pugh, P.J. Ratcliffe, C.J. Schofield, J. Biol. Chem. 278, 1802 (2003)
M.D. Jacobs, S.C. Harrison, Cell 95, 749 (1998)
F.E. Chen, D.B. Huang, Y.Q. Chen, G. Ghosh, Nature 391, 410 (1998)
T. Huxford, D.B. Huang, S. Malek, G. Ghosh, Cell 95, 759 (1998)
C.H. Croy, S. Bergqvist, T. Huxford, G. Ghosh, E.A. Komives, Protein Sci. 13, 1767 (2004)
S.M. Truhlar, J.W. Torpey, E.A. Komives, Proc. Natl. Acad. Sci. USA 103, 18951 (2006)
J. Fiaux, E.B. Bertelsen, A.L. Horwich, K. Wuthrich, Nature 418, 207 (2002)
R. Sprangers, L.E. Kay, Nature 445, 618 (2007)
Sue et al., J. Mol. Biol. 380, 917 (2008)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Dyson, H.J., Sue, SC., Wright, P.E. (2009). Functional Unfolded Proteins: How, When, Where, and Why?. In: Kuwajima, K., Goto, Y., Hirata, F., Kataoka, M., Terazima, M. (eds) Water and Biomolecules. Biological and Medical Physics, Biomedical . Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-88787-4_6
Download citation
DOI: https://doi.org/10.1007/978-3-540-88787-4_6
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-88786-7
Online ISBN: 978-3-540-88787-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)