Group 3 late embryogenesis abundant (G3LEA) proteins, which act as a well-characterized desiccation protectant in anhydrobiotic organisms, are structurally disordered in solution, but they acquire a predominantly α-helical structure during drying. Thus, G3LEA proteins are now accepted as intrinsically disordered proteins (IDPs). Their functional regions involve characteristic 11-mer repeating motifs. In the present study, to elucidate the origin of the IDP property of G3LEA proteins, we applied replica exchange molecular dynamics (REMD) simulation to a model peptide composed of two tandem repeats of an 11-mer motif and its counterpart peptide whose amino acid sequence was randomized with the same amino acid composition as that of the 11-mer motif. REMD simulations were performed for a single α-helical chain of each peptide and its double-bundled strand in a wide water content ranging from 5 to 78.3 wt%. In the latter case, we tested different types of arrangement: 1) the dipole moments of the two helices were parallel or anti-parallel and 2) due to the amphiphilic nature of the α-helix of the 11-mer motif, two types of the side-to-side contact were tested: hydrophilic-hydrophilic facing or hydrophobic-hydrophobic facing. Here, we revealed that the single chain alone exhibits no IDP-like properties, even if it involves the 11-mer motif, and the hydrophilic interaction of the two chains leads to the formation of a left-handed α-helical coiled coil in the dry state. These results support the cytoskeleton hypothesis that has been proposed as a mechanism by which G3LEA proteins work as a desiccation protectant.The traditional view of the structure-function paradigm is that a protein's function is closely related to a uniquely rigid three-dimensional (3D) structure, which is determined by the protein's primary amino acid sequence. However, it has been accepted that a number of proteins do not adopt a unique 3D structure in solution; instead, they adopt randomcoil-like conformations [1][2][3]. Such proteins undergo a disorder-to-order transition as a requirement for biological function, and they are referred to as intrinsically disordered proteins (IDPs) [1][2][3].Group 3 late embryogenesis abundant (G3LEA) proteins are disordered in solution, but they structuralize into an α-helical structure during drying. To elucidate the origin of this unusual property, we performed replica exchange MD simulations for a peptide composed of two tandem repeat of an 11-mer motif characteristic to G3LEA proteins. It was revealed that its single chain alone exhibits no structuralization, but its two-helix bundle forms a left-handed α-helical coiled coil in the dry state. These results support the cytoskeleton hypothesis that has been proposed as a mechanism by which G3LEA proteins work as a desiccation protectant in anhydrobiotic organisms.

No abstract