A conserved helix‐unfolding motif in the naturally unfolded proteins

Among the naturally unfolded proteins there are many polypeptides that retain an extended conformation in the absence of any apparent signal. Using sequence alignment and secondary structure prediction tools, a conserved (LS/SL)(D/E)(D/E)(D/E)X(E/D) motif is uncovered in the vicinity of the N‐terminus of their unfolded helices. A comparison of these data with published observations allows one to propose that the (LS/SL)(D/E)(D/E)(D/E)X(E/D) motif is a helix‐unfolding signal. Furthermore, the strong similarity between this motif and the STXXDE casein kinase II phosphorylation site suggests a regulatory mechanism for the naturally unfolded proteins within the cell. Proteins 2001;44:479–483. © 2001 Wiley‐Liss, Inc.

[1]  Smart Jl,et al.  PHOSPHORYLATION STABILIZES THE N-TERMINI OF ALPHA -HELICES , 1999 .

[2]  J. Capone,et al.  Purification and characterization of the carboxyl-terminal transactivation domain of Vmw65 from herpes simplex virus type 1. , 1992, The Journal of biological chemistry.

[3]  S. Yoo.  pH- and Ca(2+)-induced conformational change and aggregation of chromogranin B. Comparison with chromogranin A and implication in secretory vesicle biogenesis. , 1995, The Journal of biological chemistry.

[4]  J. Ávila,et al.  Physicochemical characterization of the heat-stable microtubule-associated protein MAP2. , 1986, European journal of biochemistry.

[5]  L. Kay,et al.  Solution Structure of a TBP–TAFII230 Complex Protein Mimicry of the Minor Groove Surface of the TATA Box Unwound by TBP , 1998, Cell.

[6]  C. Vinson,et al.  Phosphorylation destabilizes alpha-helices. , 1997, Nature structural biology.

[7]  A. Frankel,et al.  Costabilization of peptide and RNA structure in an HIV Rev peptide-RRE complex. , 1994, Biochemistry.

[8]  Charles Elkan,et al.  Fitting a Mixture Model By Expectation Maximization To Discover Motifs In Biopolymer , 1994, ISMB.

[9]  K. Dahlman-Wright,et al.  Structural characterization of a minimal functional transactivation domain from the human glucocorticoid receptor. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Baldwin,et al.  The active form of the steroidogenic acute regulatory protein, StAR, appears to be a molten globule. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[11]  F. Corpet.  Multiple sequence alignment with hierarchical clustering. , 1988, Nucleic acids research.

[12]  H. Nelson,et al.  Yeast heat shock transcription factor N‐terminal activation domains are unstructured as probed by heteronuclear NMR spectroscopy , 1996, Protein science : a publication of the Protein Society.

[13]  J. Davies,et al.  Molecular Biology of the Cell , 1983, Bristol Medico-Chirurgical Journal.

[14]  Peter E Wright,et al.  Solution Structure of the KIX Domain of CBP Bound to the Transactivation Domain of CREB: A Model for Activator:Coactivator Interactions , 1997, Cell.

[15]  A. Chaffotte,et al.  The anticodon-binding domain of tyrosyl-tRNA synthetase: state of folding and origin of the crystallographic disorder. , 2000, Biochemistry.

[16]  K. Fiebig,et al.  Folding intermediates of SNARE complex assembly , 1999, Nature Structural Biology.

[17]  J. Thompson,et al.  Using CLUSTAL for multiple sequence alignments. , 1996, Methods in enzymology.

[18]  M. Czisch,et al.  Structural and functional analysis of the NF-kappa B p65 C terminus. An acidic and modular transactivation domain with the potential to adopt an alpha-helical conformation. , 1994, The Journal of biological chemistry.

[19]  T. Steitz,et al.  The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. , 2000, Science.

[20]  Amos Bairoch,et al.  The PROSITE database, its status in 1999 , 1999, Nucleic Acids Res..

[21]  C. Vinson,et al.  Phosphorylation destabilizes α-helices , 1997, Nature Structural Biology.

[22]  Y. Jan,et al.  Role of ER export signals in controlling surface potassium channel numbers. , 2001, Science.

[23]  A. Gingras,et al.  4E binding proteins inhibit the translation factor eIF4E without folded structure. , 1998, Biochemistry.

[24]  B. Luisi,et al.  Oct-1 POU and octamer DNA co-operate to recognise the Bob-1 transcription co-activator via induced folding. , 1999, Journal of molecular biology.

[25]  A. Levine,et al.  Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain , 1996, Science.

[26]  C. Dobson,et al.  NMR analysis of main-chain conformational preferences in an unfolded fibronectin-binding protein. , 1997, Journal of molecular biology.

[27]  H. Dyson,et al.  Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. , 1999, Journal of molecular biology.

[28]  L. Pinna.  Casein kinase 2: an 'eminence grise' in cellular regulation? , 1990, Biochimica et biophysica acta.

[29]  P E Wright,et al.  Structure of the recombinant full-length hamster prion protein PrP(29-231): the N terminus is highly flexible. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Kevin Struhl,et al.  Folding transition in the DMA-binding domain of GCN4 on specific binding to DNA , 1990, Nature.

[31]  V. Dötsch,et al.  Solution Structure of the Core NFATC1/DNA Complex , 1998, Cell.

[32]  Sandeep Kumar,et al.  Dissecting α‐helices: Position‐specific analysis of α‐helices in globular proteins , 1998, Proteins.

[33]  G. Damaschun,et al.  Prothymosin alpha: a biologically active protein with random coil conformation. , 1995, Biochemistry.

[34]  S. Yoo,et al.  Ca2(+)-induced conformational change and aggregation of chromogranin A. , 1990, The Journal of biological chemistry.

[35]  F. Dahlquist,et al.  The C-terminal half of the anti-sigma factor FlgM contains a dynamic equilibrium solution structure favoring helical conformations. , 1998, Biochemistry.

[36]  C Combet,et al.  NPS@: network protein sequence analysis. , 2000, Trends in biochemical sciences.

[37]  E. Mandelkow,et al.  Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. , 1994, The Journal of biological chemistry.