Abstract

Earlier computational and bioinformatics analysis of several large protein datasets across 28 species showed that proteins involved in regulation and execution of programmed cell death (PCD) possess substantial amounts of intrinsic disorder. Based on the comprehensive analysis of these datasets by a wide array of modern bioinformatics tools it was concluded that disordered regions of PCD-related proteins are involved in a multitude of biological functions and interactions with various partners, possess numerous posttranslational modification sites, and have specific evolutionary patterns (Peng et al. 2013). This study extends our previous work by providing information on the intrinsic disorder status of some of the major players of the three major PCD pathways: apoptosis, autophagy, and necroptosis. We also present a detailed description of the disorder status and interactomes of selected proteins that are involved in the p53-mediated apoptotic signaling pathways.

Highlights

  • Many biologically active proteins do not have a unique 3-D structure as a whole or in part[1,2,3,4,5], and are as such described as intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and IDP regions (IDPRs)

  • We report the results of the focused evaluation of intrinsic disorder in specific sub-sets of human proteins in three major modules of the programmed cell death, namely apoptosis, necroptosis, and autophagy

  • Our previous study suggested that one of the common structural features of these programmed cell death (PCD)-related proteins is their strong propensity for being disordered or to possess long IDPRs42. We believe that this disordered nature of PCD-controlling proteins allows them to be uniquely and effectively modulated via multiple specific interaction with various partners effectively, and to control the regulation and execution of different PCD modules[42]. This conclusion is supported by a simple visualization technique used in Figure 1, namely, coding the involved proteins according to their intrinsic disorder content evaluated by PONDR-FIT

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Summary

Introduction

Many biologically active proteins do not have a unique 3-D structure as a whole or in part[1,2,3,4,5], and are as such described as intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and IDP regions (IDPRs). IDPs/IDPRs are highly abundant in virtually any given proteome[1,3,5,12] As they are abundant constituents of all cells, tissues, and organs, and are responsible for crucial controling and regulating functions, IDPs are commonly involved in the pathogenesis of various human diseases[13]. This conclusion is based on numerous case studies in which a particular IDP was shown to be associated with a particular disease (including many cancer-14–19 and neurodegeneration-related proteins20–27), as well as on the results of systematic bioinformatics studies[12,28,29,30,31,32,33,34,35,36]

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