Special Issue "Intrinsically Disordered Proteins and Chronic Diseases"
A special issue of Biomolecules (ISSN 2218-273X).
Deadline for manuscript submissions: 1 December 2018
Assoc. Prof. Dr. Vladimir N. Uversky
Molecular Medicine, University of South Florida, Tampa, USA
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Interests: intrinsically disordered proteins; protein folding; protein misfolding; partially folded proteins; protein aggregation; protein structure; protein function; protein biophysics; protein bioinformatics; conformational diseases; protein–ligand interactions; protein–protein interactions
It is now increasingly evident that a large fraction of the human proteome comprises proteins, or regions within proteins that lack a 3D structure under physiological conditions, and are referred to as intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs), respectively. Despite their lack of a stable structure, IDPs/IDPRs are involved in regulation, signaling, and control, where binding to multiple partners and high-specificity/low-affinity interactions plays a crucial role. Furthermore, intrinsic disorder is a unique structural feature that enables IDPs/IDPRs to participate in, both, one-to-many and many-to-one signaling. Since they serve as general regulators of various cellular processes, IDPs/IDPRs themselves are tightly controlled. However, when overexpressed, miss-expressed, or dysregulated, IDPs/IDPRs are prone to engage in promiscuous, often unwanted interactions and, thus, may lead to the development of various pathological states.
This Special Issue of Biomolecules is dedicated to exploring the role of IDPs in various chronic diseases. The main goal is to compile articles that describe recent progress in elucidating the mechanisms by which IDPs cause variious human diseases, such as cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases, diabetes, genetic diseases, to name just a few.
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access quarterly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 650 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
- Intrinsically Disordered Protein
- Neurodegenerative diseases
- Cardiovascular diseases
- Genetic diseases
- Protein structure
- Protein function
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
1) Mark E. Bowen, Hugo Sanabria, Tatyana Smirnova, Keith R. Weninger. Spontaneous switching between conformational ensembles in intrinsically disordered proteins.
2) Prakash Kulkarni, Mohit Jolly, Xingcheng Lin, Federico, Yanan He, Yihong Chen, Krithika Rajagopalan, Steven M. Mooney, Yu Zeng, Keith Weninger, Alex Grishaev, Jose Onuchic, Herbert Levine, Ravi Salgia, Vladimir Uversky, John Orban. Conformational dynamics of PAGE4 and phenotypic switching in prostate cancer.
3) Nagarajan Vaidehi and Supriyo Bhattacharya. Emerging multiscale computational methods for understanding the structure and function of intrinsically disordered proteins.
4) E. Brad Thompson and Raj Kumar. Role of phosphorylation in the modulation of glucocorticoid receptor’s intrinsically disordered domain.
Abstract: Protein phosphorylation often switches cellular activity from one state to another, and this post-translational modification plays an important role in the gene regulation by the nuclear hormone receptor superfamily including the glucocorticoid receptor (GR). Cell signaling pathways that regulate phosphorylation of the GR are important determinants of GR actions, including lymphoid cell apoptosis, DNA binding, interaction with coregulatory proteins, and shuttling between the cytoplasmic compartments. All major functionally important phosphorylation sites in the human GR are located in its N-terminal domain (NTD), which possesses a powerful transactivation domain, AF1. The GR NTD exists as an intrinsically disordered protein (IDP) and undergoes disorder-order transition for AF1’s efficient interaction with several coregulatory proteins and subsequent AF1-mediated GR activity. It has been reported that GR’s NTD/AF1 undergoes such disorder-order transition following site-specific phosphorylation. This review provides currently available information regarding the role of GR phosphorylation in its action and highlights the possible underlying mechanisms of action.
5) Christophe Bignon, Francesca Troilo, Stefano Gianni and Sonia Longhi. Modulation of NTAIL interactions through fuzziness and sequence features of disordered binding sites.
Abstract: In this study, we review our recent findings on the differential interaction mechanisms of NTAIL, a model viral IDP, with two of its known binding partners, i.e. XD (a globular viral protein) and hsp70 (a globular cellular protein). NTAIL binds both XD and hsp70 via a molecular recognition element (MoRE) that is flanked by two fuzzy regions. The long (85 residues) N-terminal fuzzy region is a natural dampener of the interaction with both XD and hsp70. In the case of binding to XD, the N-terminal fuzzy appendage of NTAIL reduces the rate of alpha-helical folding of the MoRE. The dampening effect of the fuzzy appendage on XD and hsp70 binding depends on the length of the N-terminal region. Despite this similarity, NTAIL binding to XD and hsp70 appears to rely on completely different requirements. Almost any substitution of the MoRE decreases XD binding, while many of them increase the binding to hsp70. In addition, XD binding is very sensitive to the alpha helical state of the MoRE while hsp70 is not. Thus, contrary to binding to hsp70, binding to XD appears to be strictly dependent on the wild-type primary and secondary structure of the MoRE but not hsp70. Finally, we include new results showing that while the stoichiometry of the NTAIL/XD interaction is a strictly 1:1, NTAIL/hsp70 stoichiometry can be 1:1, 2:1 or even 3:1. On the basis of these results, we propose a possible biotechnological use of a tandem mutated MoRE.
6) Oxana V. Galzitskaya et al. Search for functions of intrinsically disordered prion-like domains for FET proteins involved in amyotrophic lateral sclerosis and frontotemporal dementia.
7) Roopa Thapar et al. Regulation Of Macromolecular Complexes Involved In DNA Break Repair By Instrinsically Disordered Proteins.
8) Wenning Wang et al. Dynamic Interactions Between Intrinsically Disordered Proteins.
9) Ameeta Kelekar and L. Michel Espinoza-Fonseca. Noxa—an intrinsically disordered Bcl-2 protein is both tumor suppressor and promoter in T cells.
10) Matteo Lambrughi and Elena Papaleo. Effects of cancer mutations and post-translational modifications on the structural biology of the functionally relevant disordered regions of ATG9A.
11) Ibraheem Alshareedah, Jason Ngo, Taranpreet Kaur, Hannah Seppala, Priya Banerjee. Physicochemical tuning of ribonucleoprotein liquid condensation.