Intrinsically disordered protein

Intrinsic disorder might not be encoded by the sequence, but rather might be the result of the absence of suitable tertiary interactions. If this were the general cause of intrinsic disorder, any subset of ordered sequences and any subset of disordered sequences would likely be the same within the statistical uncertainty of the sampling. On the other hand, if intrinsic disorder were encoded by the amino acid sequence, any subset of disordered sequences would likely differ significantly from samples of ordered protein sequences. Thus, to test the hypothesis that disorder is encoded by the sequence, we collected examples of intrinsically ordered and intrinsically disordered proteins, then determined whether and how their sequences were distinguishable. 

Number of Proteins and Residues in Databases of Intrinsically Disordered Protein Characterized by Various Methods... 

III. PONDR Estimations of the Commonness of Intrinsically Disordered Proteins... 

Recently, there has been great interest in proteins that exhibit biological activity but lack a well-defined secondary or tertiary structure after purification (Dunker et al., 1998, 2001 Schweers et al., 1994 Uversky et al., 2000 Wright and Dyson, 1999). Such proteins are referred to as intrinsically disordered or unstructured. An analysis in 1998 of the Swiss Protein Database revealed that about 15,000 proteins in that database are likely to contain disordered segments at least 40 residues in length (Romero et al., 1998). Dyson and Wright (2002) review intrinsically disordered proteins in this volume. 

There are now numerous examples of proteins that are unstructured or only partially structured under physiological conditions yet are nevertheless functional (Dunker and Obradovic, 2001 Wright and Dyson, 1999). In many cases, such intrinsically disordered proteins adopt folded structures upon binding to their biological targets. As the proteins that constitute the transcriptional machinery have become... 

Although MC is an underutilized tool in the field of computational molecular biophysics, there are beneficial features that can be exploited, especially in conjunction with implicit solvent models. Specifically, MC has the potential of accessing length scales that are inaccessible to MD in complex phenomena like peptide aggregation or conformational sampling of intrinsically disordered proteins. 

P. Tompa, Structure and Function of Intrinsically Disordered Proteins. CRC Press, 2009. 

Folding of an Intrinsically Disordered Protein Upon Binding to a Target... 

Coupled folding and binding is a frequent theme in the field of intrinsically disordered proteins (see Chap. 6). One of the earliest examples of this phenomenon was the interaction of the phosphorylated kinase-inducible domain (pKID) of the transcription factor CREB with the KIX domain of the transcriptional coactivator CBP. Free pKID is unfolded in solution [21], but folds into an orthogonal pair of helices, aA and aB, upon binding to the folded KIX domain (Fig. 1.5) [23]. We have recently posed the question, what is the... 

Radivojac P, Obradovic Z, Smith DK, Zhu G, Vucetic S, Brown CJ, Lawson JD, Dunker AK (2004) Protein flexibility and intrinsic disorder. Protein Sci 13 71-80... 

Peti W, Nairn AC, Page R (2012) Folding of intrinsically disordered protein phosphatase 1 regulatory proteins. Curr Phys Chem 2 107-114... 

The binding of metal ions to PrP is not surprising if one takes the nature of intrinsically disordered proteins into account. As discussed above, these structural elements explore conformational space in order to find an appropriate binding partner. Obviously, the N-terminal sequence of PrP is such that it can easily accommodate two-valent cations. Whether these data have functional relevance remains to be proven. 

Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CR, Hipps KW, Ausio J, Nissen MS, Reeves R, Kang CH, Kissinger CR, Bailey RW, Griswold MD, Chiu M, Gamer EC, Obradovic Z (2001) Intrinsically disordered protein. J Mol Graph Model 19 26-59... 

Narayanan RL, Diirr UHN, Bibow S, Biemat J, Mandelkow E, Zweckstetter M (2010) Automatic assignment of the intrinsically disordered protein Tau with 441-residues. J Am Chem Soc 132 11906-11907... 

Spectra of denatured proteins and intrinsically disordered proteins show high peak overlap due to very low dispersions of signal frequencies, making sparse sampling methods a prerequisite for successful analysis. Examples are a 60-residue fragment of nucleoprotein N from the paramyxovirus Sendai [28] the 148-residue outer membrane protein X (OmpX) from Escherichia coli [29] a 115-residue CD3 Z domain [24] a 81-residue delta-subunit of RNA polymerase from Bacillus subtilis [30] the 441-residue, intrinsically disordered protein Tau [31] the 70-residue N-terminal domain of SKIP [32]. 

Eliezer D (2009) Biophysical characterization of intrinsically disordered proteins. Curr Opin Struct Biol 19 23-30... 

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