Co-evolution of proteins and solutions: protein adaptation versus cytoprotective micromolecules and their roles in marine organisms

Abstract

Organisms experience a wide range of environmental factors such as temperature, salinity and hydrostatic pressure, which pose challenges to biochemical processes. Studies on adaptations to such factors have largely focused on macromolecules, especially intrinsic adaptations in protein structure and function. However, micromolecular cosolutes can act as cytoprotectants in the cellular milieu to affect biochemical function and they are now recognized as important extrinsic adaptations. These solutes, both inorganic and organic, have been best characterized as osmolytes, which accumulate to reduce osmotic water loss. Singly, and in combination, many cosolutes have properties beyond simple osmotic effects, e.g. altering the stability and function of proteins in the face of numerous stressors. A key example is the marine osmolyte trimethylamine oxide (TMAO), which appears to enhance water structure and is excluded from peptide backbones, favoring protein folding and stability and counteracting destabilizers like urea and temperature. Co-evolution of intrinsic and extrinsic adaptations is illustrated with high hydrostatic pressure in deep-living organisms. Cytosolic and membrane proteins and G-protein-coupled signal transduction in fishes under pressure show inhibited function and stability, while revealing a number of intrinsic adaptations in deep species. Yet, intrinsic adaptations are often incomplete, and those fishes accumulate TMAO linearly with depth, suggesting a role for TMAO as an extrinsic 'piezolyte' or pressure cosolute. Indeed, TMAO is able to counteract the inhibitory effects of pressure on the stability and function of many proteins. Other cosolutes are cytoprotective in other ways, such as via antioxidation. Such observations highlight the importance of considering the cellular milieu in biochemical and cellular adaptation.

Elevated osmolytes in rainbow smelt: the effects of urea, glycerol and trimethylamine oxide on muscle contractile properties

“…5. concentrations of 0.6 mol l −1 urea and 0.2 mol l −1 TMAO (Kumemoto et al, 2012). Yancey and Siebenaller (2015) reviewed the roles of TMAO, urea and glycerol, along with several other osmolytes, in cytoprotection. They reported that the counteracting effects of TMAO and urea are related to the differing effects of the two osmolytes on peptide backbone exposure to water.…”

“…TMAO acts to stabilize protein structure by forming complexes with water that promote the exclusion of water from the protein backbone (Zou et al, 2002;Canchi and García, 2013). Similar to TMAO, glycerol is predicted to act as a stabilizer of protein structure (Yancey and Siebenaller, 2015). These authors note that while the negative effects of urea in destabilizing protein structure and reducing measures of enzyme function are understood, it is also important to recognize that stabilization is not by definition beneficial (Yancey and Siebenaller, 2015).…”

“…Similar to TMAO, glycerol is predicted to act as a stabilizer of protein structure (Yancey and Siebenaller, 2015). These authors note that while the negative effects of urea in destabilizing protein structure and reducing measures of enzyme function are understood, it is also important to recognize that stabilization is not by definition beneficial (Yancey and Siebenaller, 2015). TMAO has a negative impact on actinmyosin sliding velocity (Kumemoto et al, 2013) and LDH activity is reduced in the presence of glycerol and TMAO (Fields et al, 2001;Yancey and Siebenaller, 2015).…”

“…These authors note that while the negative effects of urea in destabilizing protein structure and reducing measures of enzyme function are understood, it is also important to recognize that stabilization is not by definition beneficial (Yancey and Siebenaller, 2015). TMAO has a negative impact on actinmyosin sliding velocity (Kumemoto et al, 2013) and LDH activity is reduced in the presence of glycerol and TMAO (Fields et al, 2001;Yancey and Siebenaller, 2015). TMAO and urea also have counteracting impacts on actin polymerization (Rosin et al, 2015), suggesting that these osmolytes may have very broad influences on the biology of smelt and other organisms that employ them for osmoregulation and cytoprotection.…”

“…Some research suggests that urea and TMAO affect the actin-myosin interaction in different ways and balance each other (Kumemoto et al, 2012). TMAO is known to support protein folding, while urea is a protein inhibitor (Yancey, 2005;Yancey and Siebenaller, 2015). Urea appears to enhance freeze survival and preserve muscle function during recovery from winter in wood frogs (Costanzo et al, 2008(Costanzo et al, , 2013.…”