Water-Mediated Protein-Protein Interactions at High Pressures are Controlled by a Deep-Sea Osmolyte

Abstract

The influence of natural cosolvent mixtures on the pressure-dependent structure and protein-protein interaction potential of dense protein solutions is studied and analyzed using small-angle X-ray scattering in combination with a liquid-state theoretical approach. The deep-sea osmolyte trimethylamine-N-oxide is shown to play a crucial and singular role in its ability to not only guarantee sustainability of the native protein's folded state under harsh environmental conditions, but it also controls water-mediated intermolecular interactions at high pressure, thereby preventing contact formation and hence aggregation of proteins.

Pressure Sensitivity of SynGAP/PSD‐95 Condensates as a Model for Postsynaptic Densities and Its Biophysical and Neurological Ramifications

“…Considering that the pressure dependence of pairwise binding is insufficient to account for the pressure sensitivity of SynGAP/PSD-95 droplets, ap lausible physicalr ationalization is that as ignificant larger void (cavity)v olumei naccessible to water molecules is associated with the multiple-molecule interaction network in the condensed phase than the dilute phase of SynGAP/PSD-95. In general, void volume can arise geometrically from imperfect packing in compactc onformational states, [13] as in the folded structures of globular proteins. [21,[43][44][45] Void-volume effects can offer ar ationalizationf or pressure-dependentL LPS of biomolecular condensates as well, wherein the voids are envisioned to be transientw hereas the voids in folded proteins are essentially static.…”

“…[5,10,12] By comparison, high hydrostatic pressure (HHP) as as tress factor for biomolecular LLPS is much less explored. [7,[13][14][15] Yet, a large fraction of the earth biosphere thrives under HHP,r eaching pressures up to about 1kbar (100 MPa, % 1000 atm) in the deep sea and even beyond in the sub-seafloorc rust. [16,17] HHP studies on biomolecular condensates are thus necessary for understanding the physical basis of extant life in the deep sea, which might also be the birth place of life on earth.…”

“…[18][19][20][21][22][23][24][25] Seekingp rogress in this context, we recently started investigating effects of pressureo n the LLPS of simple one-component protein systems, such as lysozyme, a-elastin, g-crystallin, and the intrinsically disordered region of the DEAD-box helicaseD dx4. [7,[13][14][15] Here, we explore am ore complex aqueous system consisting of two major proteins of the postsynaptic densities in neurons.…”

Stability of the chaperonin system GroEL–GroES under extreme environmental conditions

“…Accumulation of particular cosolutes, such as methylamines, polyols and amino acids, are often found in cells to equilibrate cellular osmotic pressure and to maintain stability and functionality of proteins and their assemblies. [17][18][19][20]40 Therefore, such small organic molecules are termed osmolytes or chemical chaperones. A prominent and effective osmolyte, trimethylamine-N-oxide (TMAO), is even found in tissue of various deep sea animals and its concentration correlates with the ocean depth, i.e.…”

“…15 Interestingly, a relatively high concentration of particular osmolytes, such as trimethylamine-N-oxide (TMAO), was found in cells of deep sea organisms, which are thought to help rescuing cells from pressure-induced deterioration, including protein unfolding at high hydrostatic pressures. [17][18][19][20] Hence, HHP studies on biomolecular systems are prerequisite for understanding current and ancient life in the deep sea, an environment which is also the potential birth place of life on Earth. 13,14 Remarkably, very little is known about the temperature and pressure stability of the chaperonin system and the effect of cosolutes on its stability.…”