Intrinsically disordered protein: Part I

Abstract

This article presents various features related to a strange, yet extremely important group of proteins called intrinsically disordered proteins (IDPs) which used to be and are still by some called generically “unstructured” proteins. Huge abundance (~30% of the entire human proteome) of IDPs has brought a critical paradigm shift in protein science as well as in structural biology during the last three decades. In this article a brief introduction on these unorthodox proteins will be followed by an explanation for “the long-and-winding” journey to reach the consensus name of IDP. The term IDP was adopted with difficulty only in 2012 after 20 years since the first discovery reports on “unstructured” proteins had appeared. Next, some comments will be made on the hurdles encountered in the early days to have the concept of “unstructured” proteins or the manuscripts dealing with them accepted in the protein science field. Thirdly, the saga by the KRIBB NMR team to establish the pre-structured motifs (PreSMos) that are the transient secondary structures observed in the target unbound state of IDPs as the target-binding active sites of IDPs will be delineated in depth along with the relevant publications. Finally, the issues that need to be explored further in the IDP field such as AlphaFold will be discussed.