Protein disorder - function paradigm: Putative role in inflammation

TL;DR

This paper explores how disordered proteins, which lack a fixed structure, may play a role in inflammation and aging-related diseases.

Contribution

The paper introduces the disorder-function paradigm and its potential role in immunological processes like inflammAging.

Findings

Intrinsically disordered proteins (IDPs) are structurally unstable and dynamic.

IDPs are a major part of the 'dark' proteome and influence cellular processes.

The disorder-function paradigm may mediate chronic inflammation and aging-related diseases.

Abstract

Traditional protein biochemistry defends the intimate interdependence between protein function and structure, the latter being
consisting of four distinct levels: premary sstructure: viz, the sequence of its constituent amino acids linked by
peptides bonds - the polypeptide chain; ssecondary structure: viz, localized folding patterns (e.g.,
a α-helix, β-sheets) of the polypeptide chain held by hydrogen bonds between amino acid backbones; tertiary structure:
viz, three-dimensional folding of the protein held by interactions between amino acid side chains mediated by disulfide
bridges, hydrogen bonds, ionic bonds and hydrophobic interactions; and quaternary structure: viz, attachment of
subunits, when appropriate, by means of similar chemical interactions to form a functional protein complex. Research evidence in the
last decade has described intrinsically disordered proteins (IDPs) as polypeptides that lack a well-defined three/four-dimensional
structure under physiological conditions, appear structurally unstable and manifest in a dynamic set of possible conformations. IDPs are
a major component of the "dark" proteome, genome protein products not yet characterized through experimental structure determination and
existing homology modeling. Dark proteome in general and IDPs specifically define and characterize the novel disorder - function
paradigm, which critically mediate and modulate key cellular organelles and pathways and influence physiopathological processes from
aging to chronic diseases and pathogen infection. The role of the disorder-function paradigm in the immunome and the inflammasome in
general and specifically in the process of chronic metabolic inflammation observed in aging - i.e., inflammAging - could
be elucidated through diverse AI platforms.