Unfoldomics of human diseases: linking protein intrinsic disorder with diseases
Vladimir N. Uversky,Vladimir N. Uversky,Christopher J. Oldfield,Uros Midic,Hongbo Xie,Bin Xue,Slobodan Vucetic,Lilia M. Iakoucheva,Zoran Obradovic,A. Keith Dunker +9 more
TLDR
Unfoldomics of human diseases utilizes unrivaled bioinformatics and experimental techniques, paves the road for better understanding of human Diseases, their pathogenesis and molecular mechanisms, and helps develop new strategies for the analysis of disease-related proteins.Abstract:
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 are frequently used to tune the IDP functionality. Several individual IDPs were shown to be associated with human diseases, such as cancer, cardiovascular disease, amyloidoses, diabetes, neurodegenerative diseases, and others. This raises questions regarding the involvement of IDPs and IDRs in various diseases.read more
Citations
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Journal ArticleDOI
Classification of intrinsically disordered regions and proteins.
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Characterization of unannotated and uncharacterized protein segments is expected to lead to the discovery of novel functions as well as provide important insights into existing biological processes and is likely to shed new light on molecular mechanisms of diseases that are not yet fully understood.
Journal ArticleDOI
Understanding protein non-folding.
TL;DR: This review describes the family of intrinsically disordered proteins, members of which fail to form rigid 3-D structures under physiological conditions, either along their entire lengths or only in localized regions.
Classification of Intrinsically Disordered Regions and Proteins
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Uncharacterized and uncharacterized protein segments are likely to be a large source of functional novelty relevant for discovering new biology as discussed by the authors, which is likely to lead to the discovery of novel functions as well as provide important insights into existing biological processes.
Journal ArticleDOI
Introducing Protein Intrinsic Disorder.
Johnny Habchi,Peter Tompa,Peter Tompa,Sonia Longhi,Sonia Longhi,Vladimir N. Uversky,Vladimir N. Uversky +6 more
TL;DR: This paper presents a meta-anatomy of the determinants of Macromolećules Biologiques, a probabilistic framework for estimating the number of components in a Response to Enzymology.
Journal ArticleDOI
A decade and a half of protein intrinsic disorder: Biology still waits for physics
TL;DR: Some of the recent advances in this exciting field of intrinsically disordered proteins are summarized and some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs are considered.
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