A decade and a half of protein intrinsic disorder: Biology still waits for physics

By Vladimir N Uversky. 2013

470 citations recorded by the source corpus.

The abundant existence of proteins and regions that possess specific functions without being uniquely folded into unique 3D structures has become accepted by a significant number of protein scientists. Sequences of these intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number of specific features, such as low overall hydrophobicity and high net charge which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic volumes, low contents of ordered secondary structure, and are characterized by high structural heterogeneity. They are very flexible, but some may undergo disorder to order transitions in the presence of natural ligands. The degree of these structural rearrangements varies over a very wide range. IDPs/IDPRs are tightly controlled under the normal conditions and have numerous specific functions that complement functions of ordered proteins and domains. When lacking proper control, they have multiple roles in pathogenesis of various human diseases. Gaining structural and functional information about these proteins is a challenge, since they do not typically “freeze” while their “pictures are taken.” However, despite or perhaps because of the experimental challenges, these fuzzy objects with fuzzy structures and fuzzy functions are among the most interesting targets for modern protein research. This review briefly summarizes some of the recent advances in this exciting field and considers some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs.

Subfields: Materials Chemistry, Molecular Biology

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Citations in the corpus

Critical assessment of methods of protein structure prediction (CASP) — round x (2013, methodology): “…effectiveness of meth-ods for predicting which parts of a protein do not exhibit a single 3D structure—that is, they are in some sense disordered.35 Although there has been little change in the accuracy of methods for six rounds of CASP, their importance in the real world of modeling continues…”
Intrinsic disorder here, there, and everywhere, and nowhere to escape from it (2017, background): “There is also a shift in recognizing the position of IDPs within the protein universe, from the original opposition of disorder to order and disorder-based functions to classical order-based protein functions [2, 8–10] to the acknowledgement that there is a broad spectrum of protein flexibility, spa”
Intrinsically Disordered Proteins Studied by NMR Spectroscopy (2015, background): “Intrinsically disordered proteins (IDPs) play crucial roles in many aspects of molecular and cell biology, as these proteins are involved in a variety of signalling and regulation processes as well as being implicated in a range of neurodegenerative and systemic disorders such as Alzheimer’s and Par”
p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure–Function Continuum Concept (2016, background): “Although they are without stable 3D structures, IDPs/IDPRs play a number of crucial functional roles in living organisms, especially in vital biological processes, such as control, signaling, recognition, and regulation [2,3,7,20,21,25,26].”