Intrinsically unstructured proteins and their functions
Nature Reviews Molecular Cell BiologyPublished 1 March 2005
H. Jane Dyson, Peter E. Wright
Citations3,878
SJR quartileQ1
SJR score37.35
SNIP20.23
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TL;DR
Many gene sequences in eukaryotic genomes encode entire proteins or large segments of proteins that lack a well-structured three-dimensional fold, whereas others constitute flexible linkers that have a role in the assembly of macromolecular arrays.
Abstract
Many gene sequences in eukaryotic genomes encode entire proteins or large segments of proteins that lack a well-structured three-dimensional fold. Disordered regions can be highly conserved between species in both composition and sequence and, contrary to the traditional view that protein function equates with a stable three-dimensional structure, disordered regions are often functional, in ways that we are only beginning to discover. Many disordered segments fold on binding to their biological targets (coupled folding and binding), whereas others constitute flexible linkers that have a role in the assembly of macromolecular arrays.
Keywords
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Proceedings of the National Academy of SciencesStructure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway
196 Citations2002Charles E. Dann, Richard K. Bruick +1 more
The structure of factor-inhibiting HIF-1 (FIH-1), the pertinent asparaginyl hydroxylase involved in hypoxic signaling, is presented and the presence of a FIH- 1 homodimer that forms in solution and is essential for FIH activity is revealed.
NatureAltered protein conformation on DNA binding by Fos and Jun
193 Citations1990Lekha Patel, Cory Abate +1 more
Assessment systems using fluorescence spectroscopy and circular dichroism to monitor dimerization and DNA binding directly indicate that the interaction of Fos and Jun with DNA results in an altered conformation of the protein dimers and an increased α-helical content.
Journal of Molecular BiologySolution structure of the first three zinc fingers of TFIIIA bound to the cognate DNA sequence: determinants of affinity and sequence specificity
184 Citations1997Deborah S. Wuttke, Mark P. Foster +3 more
The high resolution solution structure of a protein containing the three amino-terminal zinc fingers of Xenopus laevis transcription factor IIIA bound to its cognate DNA duplex was determined by nuclear magnetic resonance spectroscopy and provides a molecular level explanation for the large body of footprinting and mutagenesis data available for the TFIIIA-DNA complex.
Journal of Biological ChemistryCooperativity in Transcription Factor Binding to the Coactivator CREB-binding Protein (CBP)
179 Citations2002Natalie K. Goto, Tsaffrir Zor +3 more
The characterization of ternary complexes formed by the KIX domain of CBP and the transactivation domain of the trithorax group protein mixed lineage leukemia protein (MLL) and either the phosphorylated kinase-inducible domain (pKID) of CREB or the activation domain from c-Myb is reported.
Journal of Molecular RecognitionRecognition between flexible protein molecules: induced and assisted folding
173 Citations2001Alexander P. Demchenko
This review focuses on a very important but little understood type of molecular recognition — the recognition between highly flexible molecular structures that is frequent in formation of different protein–protein and protein–nucleic acid complexes.
Molecular CellICAT Inhibits β-Catenin Binding to Tcf/Lef-Family Transcription Factors and the General Coactivator p300 Using Independent Structural Modules
166 Citations2002Danette L. Daniels, William I. Weis
In the canonical Wnt signaling pathway, beta-catenin activates target genes through its interactions with Tcf/Lef-family transcription factors and additional transcriptional coactivators, and the C-terminal armadillo repeats of beta- catenin may be an attractive target for compounds designed to disrupt aberrant beta-Catenin-mediated transcription associated with various cancers.
Genes to CellsRoles of partly unfolded conformations in macromolecular self‐assembly
164 Citations2001Keiichi Namba
Various aspects of mechanistic roles of natively unfolded conformations of proteins are overviewed and discussed in this short review.
Journal of Biological ChemistryRoles of Phosphorylation and Helix Propensity in the Binding of the KIX Domain of CREB-binding Protein by Constitutive (c-Myb) and Inducible (CREB) Activators
162 Citations2002Tsaffrir Zor, B Mayr +3 more
NMR and biochemical analyses are used to study the interactions of KIX with the trans activation domain from the constitutive activator c-Myb and with the kinase-inducible transactivation domain (KID) from CREB to obtain insights into the mechanism by which the KIX domain of CBP can recognize the transactivation domains of many different transcription factors.
Journal of Molecular BiologyDNA-induced α-helix capping in conserved linker sequences is a determinant of binding affinity in Cys2-His2 zinc fingers
151 Citations2000John H. Laity, H. Jane Dyson +1 more
NMR evidence is presented for another contribution to high-affinity binding, a highly specific DNA-induced helix capping involving residues in the linker sequence between fingers, which is suggested to provide a rationale for the high conservation of the TGEKP linker sequences in Cys2-His2 zinc finger proteins.
FEBS LettersConformational preferences in the Ser<sup>133</sup>‐phosphorylated and non‐phosphorylated forms of the kinase inducible transactivation domain of CREB
147 Citations1998Ishwar Radhakrishnan, Gabriela C. Pérez-Alvarado +2 more
Heteronuclear NMR spectroscopic analyses reveal that the KID domain is largely unstructured except for residues that comprise the αA helix in the pKID‐KIX complex, which populate helical conformations to a significant extent.
Proteins Structure Function and BioinformaticsHost‐guest scale of left‐handed polyproline II helix formation
139 Citations2003Adam L. Rucker, Cara T. Pager +3 more
The PPII helix‐forming propensity scale will prove useful in future studies of the conformational properties of proline‐rich sequences as well as provide insights into the prevalence of PPII helices in protein unfolded states.
FEBS LettersReduced amino acid alphabet is sufficient to accurately recognize intrinsically disordered protein
133 Citations2004Edward A. Weathers, Michael E. Paulaitis +2 more
It is found that a SVM that incorporates only amino acid composition has a recognition accuracy of 87 ± 2%.
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