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Intrinsically disordered proteins: structural and functional dynamics

Authors Wallin S

Received 5 July 2016

Accepted for publication 13 October 2016

Published 17 February 2017 Volume 2017:8 Pages 7—16

DOI https://doi.org/10.2147/RRB.S57282

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 5

Editor who approved publication: Professor Zvi Kelman

Stefan Wallin

Department of Physics and Physical Oceanography, Memorial University of Newfoundland, St. John’s, NL, Canada

Abstract: The classical view holds that proteins fold into essentially unique three-dimensional structures before becoming biologically active. However, studies over the last several years have provided broad and convincing evidence that some proteins do not adopt a single structure and yet are fully functional. These intrinsically disordered proteins (IDPs) have been found to be highly prevalent in many genomes, including human, and play key roles in central cellular processes, such as regulation of transcription and translation, cell cycle, and cell signaling. Moreover, IDPs are overrepresented among proteins implicated in disease, including various cancers and neurodegenerative disorders. Intense efforts, by using both experimental and computational approaches, are consequently under way to uncover the molecular mechanisms that underpin the roles of IDPs in biology and disease. This review provides an introduction to the general biophysical properties of IDPs and discusses some of the recent emerging areas in IDP research, including the roles of IDPs in allosteric regulation, regulatory unfolding, and formation of intracellular membrane-less organelles. In addition, recent attempts at therapeutic targeting of IDPs by small molecules, noting in particular that IDPs represent a potentially important source of new drug targets in light of their central role in protein–protein interaction networks, are also reviewed.

Keywords: natively unfolded proteins, unstructured proteins, protein folding, protein–protein interaction, cell regulation, signaling, drug development, inhibitors

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