Wrecked regulation of intrinsically disordered proteins in diseases: pathogenicity of deregulated regulators

Abstract

Biologically active proteins without stable tertiary structure are common in all known proteomes. Functions of these intrinsically disordered proteins (IDPs) are typically related to regulation, signaling, and control. Cellular levels of these important regulators are tightly regulated by a variety mechanisms ranging from firmly controlled expression to precisely targeted degradation. Functions of IDPs are controlled by binding to specific partners, alternative splicing, and posttranslational modifications among other means. In the norm, right amounts of precisely activated IDPs have to be present in right time at right places. Wrecked regulation brings havoc to the ordered world of disordered proteins, leading to protein misfolding, misidentification, and missignaling that give rise to numerous human diseases, such as cancer, cardiovascular disease, neurodegenerative diseases, and diabetes. Among factors inducing pathogenic transformations of IDPs are various cellular mechanisms, such as chromosomal translocations, damaged splicing, altered expression, frustrated posttranslational modifications, aberrant proteolytic degradation, and defective trafficking. This review presents some of the aspects of deregulated regulation of IDPs leading to human diseases.

Structural predictions of neurobiologically relevant G-protein coupled receptors and intrinsically disordered proteins

“…192 able -the b2 adrenergic receptor/S-Carazolol (b2 AR/S-Car) -193 reproduced the results of full atomistic MD simulations[52,53].194 Importantly, our method proved to be able to recover the ori-195 entation of the S-Car ligand as in the X-e.g. GROMACS [57] and ESPRESSO [55].…”

“…Ref. [191,192] in their biological function as well as ligand binding, a process 654 which is so far not well understood [193]. 655 …”

Identification and functional characterization of grapevine transporters that mediate glucose-6-phosphate uptake into plastids

“…This phenomenon is sometimes observed in transcripts that undergo alternative splicing (Uversky 2014). Much like the remaining VvGPT2 splicing variants, VvGPTa is mostly expressed in autotrophic tissues.…”

On the potential of using peculiarities of the protein intrinsic disorder distribution in mitochondrial cytochromebto identify the source of animal meats

“…61,66,67 These proteins are commonly found in nature, 53,[68][69][70] and many of them are involved in the pathogenesis of various human diseases. [71][72][73] IDPs are more frequently observed in eukaryotes than in prokaryotes. 53,[68][69][70] Furthermore, the highest ratio of IDPs (47%) was found in nuclear proteins, with the average disorder level of transcription factors being as high as 63%.…”