Koenig Santana (woodzephyr8)

In this chapter, we review some of the known cysteine-containing protein domains categorized based on the number of cysteines they possess. We show that many protein domains contain disordered sequences interspersed with cysteines. We show that a positive correlation exists between the degree of cysteines and disorder within the sequences that flank them. Furthermore, based on the computational platform, IUPred2A, we show that cysteine-rich sequences display significant disorder in the reduced but not the oxidized form, increasing the potential for such sequences to function in a redox-sensitive manner. Overall, this chapter provides insights into an exquisite evolutionary design wherein disordered sequences with interspersed cysteines enable potential modulatory protein functions under stress and environmental conditions, which thus far remained largely inconspicuous.The double face of nickel, being both a toxic element for living organisms and a necessary metal for enzymatic reactions, forces nickel-dependent organisms to develop regulatory networks in order to tightly control the intracellular Ni(II) ion quota, avoiding the occurrence of a free Ni(II) pool and overcoming the natural scarcity of this metal ion in the environment. Among nickel-dependent enzymes, urease is an important virulence factor, being required by pathogens for host colonization and virulence. Regulation of urease activity by bacteria occurs at different levels, such as transcription, maturation and a catalysis. The regulatory networks controlling urease production and activity rely on intrinsically disordered proteins or regions. Different degrees of protein flexibility of Ni(II)-sensors influence their interactions with DNA, as well as modulate the protein-protein interactions for urease activation and the accessibility of the substrate for the catalytic activity. This chapter focuses on the molecular basis of the conformational changes and interactions based on the structural (and unstructural) information available. Understanding the role of intrinsic disorder for these regulatory networks might be the first step to design possible antimicrobial strategies aimed at identifying new selective drugs for bacterial eradication.Autophagy is a major catabolic pathway that must be tightly regulated to maintain cellular homeostasis. Protein intrinsic disorder provides a very suitable conformation for regulation; accordingly, the molecular machinery of autophagy is significantly enriched in intrinsically disordered proteins and protein regions (IDPs/IDPRs). Despite experimental challenges that the characterization of IDPRs encounters, remarkable progress has been made in recent years in revealing various roles of IDPs/IDPRs in autophagy. This chapter describes the autophagy pathway from a specific point of view, that of IDPRs. It focuses in detail on structural and mechanistic functions in autophagy that are executed by disordered regions. Via a description of autophagosome biogenesis, linking the cargo to the autophagy machinery, as well as a discussion of certain post-translational regulations, this review reveals many indispensable roles of IDPRs in the functional autophagy pathway. Devastating pathologies such as neurodegeneration, cancer, or diabetes have been linked to a malfunction in IDPs/IDPRs. The same pathologies are associated with dysfunctional autophagy, indicating that autophagic IDPRs may be a paramount causative factor. Several disease-related mechanisms of the autophagy pathway involving protein intrinsic disorder are reported in this chapter, to illustrate a wide-ranging potential of IDPRs in the therapeutic modulation of autophagy.During animal development, HOX transcription factors determine the fate of developing tissues to generate diverse organs and appendages. The power of these proteins is striking mis-expressing a HOX protein causes homeotic transformation of one body part into another. During development, HOX proteins interpret t