Abundance of Intrinsic Disorder in Protein Associated with Cardiovascular Disease
Document Type
Article
Publication Date
2006
Keywords
Cell Signaling, Chemical Vapor Deposition, Diseases and Disorders, Monomers, Peptides and Proteins
Digital Object Identifier (DOI)
https://doi.org/10.1021/bi060981d
Abstract
Evidence that many protein regions and even entire proteins lacking stable tertiary and/or secondary structure in solution (i.e., intrinsically disordered proteins) might be involved in protein−protein interactions, regulation, recognition, and signal transduction is rapidly accumulating. These signaling proteins play a crucial role in the development of several pathological conditions, including cancer. To test a hypothesis that intrinsic disorder is also abundant in cardiovascular disease (CVD), a data set of 487 CVD-related proteins was extracted from SWISS-PROT. CVD-related proteins are depleted in major order-promoting residues (Trp, Phe, Tyr, Ile, and Val) and enriched in some disorder-promoting residues (Arg, Gln, Ser, Pro, and Glu). The application of a neural network predictor of natural disordered regions (PONDR VL-XT) together with cumulative distribution function (CDF) analysis, charge−hydropathy plot (CH plot) analysis, and α-helical molecular recognition feature (α-MoRF) indicator revealed that CVD-related proteins are enriched in intrinsic disorder. In fact, the percentage of proteins with 30 or more consecutive residues predicted by PONDR VL-XT to be disordered was 57 ± 4% for CVD-associated proteins. This value is close that described earlier for signaling proteins (66 ± 6%) and is significantly larger than the content of intrinsic disorder in eukaryotic proteins from SWISS-PROT (47 ± 4%) and in nonhomologous protein segments with a well-defined three-dimensional structure (13 ± 4%). Furthermore, CDF and CH-plot analyses revealed that 120 and 36 CVD-related proteins, respectively, are wholly disordered. This high level of intrinsic disorder could be important for the function of CVD-related proteins and for the control and regulation of processes associated with cardiovascular disease. In agreement with this hypothesis, 198 α-MoRFs were predicted in 101 proteins from the CVD data set. A comparison of disorder predictions with the experimental structural and functional data for a subset of the CVD-associated proteins indicated good agreement between predictions and observations. Thus, our data suggest that intrinsically disordered proteins might play key roles in cardiovascular disease.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Biochemistry, v. 45, issue 35, p. 10448-10460
Scholar Commons Citation
Cheng, Yugong; LeGall, Tanguy; Oldfield, Christopher J.; Dunker, A. Keith; and Uversky, Vladimir N., "Abundance of Intrinsic Disorder in Protein Associated with Cardiovascular Disease" (2006). Molecular Medicine Faculty Publications. 764.
https://digitalcommons.usf.edu/mme_facpub/764
