Letter to the Editor: No folding upon binding of intrinsically disordered proteins: Still interesting but not unique and novel. A commentary on “A novel mode of interaction between intrinsically disordered proteins. by Hibino, E. and Hoshino, M., Biophysics and Physicobiology 17, 86–93 (2020). DOI: 10.2142/biophysico.BSJ-2020012”

Abstract

The emergence of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) has introduced a new paradigm of coupled binding and folding that suggests that IDPs and IDRs fold upon binding to their partners [1]. However, in 2004, a novel and previously unrecognized no folding upon binding mechanism has been first reported for several IDPs-cytoplasmic domains of signaling subunits from different cell receptors: ζ cyt , CD3δ cyt , CD3ε cyt , CD3γ cyt , FcRγ cyt , Igα cyt and Igβ cyt [2]. The IDPs studied in this work were all found to form specific homodimers under physiological conditions without folding upon dimerization [2]. This unusual phenomenon is distinct from non-specific aggregation behavior seen in many systems (e.g., elastin [3]). Later, in 2007, the no folding upon binding mechanism has been demonstrated for the heterodimeric complex of the well-folded simian immunodeficiency virus (SIV) Nef protein and intrinsically disordered ζ cyt where ζ cyt