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Protein Disorder In The Human Diseasome: Unfoldomics Of Human Genetic Diseases, Uros Midic, Christopher J. Oldfield, A. Keith Dunker, Zoran Obradovic, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Background: Intrinsically disordered proteins lack stable structure under physiological conditions, yet carry out many crucial biological functions, especially functions associated with regulation, recognition, signaling and control. Recently, human genetic diseases and related genes were organized into a bipartite graph (Goh KI, Cusick ME, Valle D, Childs B, Vidal M, et al. (2007) The human disease network. Proc Natl Acad Sci U S A 104: 8685–8690). This diseasome network revealed several significant features such as the common genetic origin of many diseases.

Methods and findings: We analyzed the abundance of intrinsic disorder in these diseasome network proteins by means of several …

Unfoldomics Of Human Diseases: Linking Protein Intrinsic Disorder With Diseases, Vladimir N. Uversky, Christopher J. Oldfield, Uros Midic, Hongbo Xie, Bin Xue, Slobodan Vucetic, Lilia M. Iakoucheva, Zoran Obradovic, A. Keith Dunker

Molecular Medicine Faculty Publications

Background: Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) lack stable tertiary and/or secondary structure yet fulfills key biological functions. The recent recognition of IDPs and IDRs is leading to an entire field aimed at their systematic structural characterization and at determination of their mechanisms of action. Bioinformatics studies showed that IDPs and IDRs are highly abundant in different proteomes and carry out mostly regulatory functions related to molecular recognition and signal transduction. These activities complement the functions of structured proteins. IDPs and IDRs were shown to participate in both one-to-many and many-to-one signaling. Alternative splicing and posttranslational modifications …