Calculation of the relative metastabilities of proteins in subcellular compartments of Saccharomyces cerevisiae

TL;DR

This paper models the metastable equilibrium of proteins in yeast cell compartments using thermodynamics, revealing how environmental factors like oxygen influence protein stability and interactions.

Contribution

It introduces a thermodynamic framework to analyze protein distributions and interactions across subcellular compartments in yeast cells.

Findings

Protein stability varies with oxygen fugacity across compartments.

Actin proteins dominate at high oxygen levels, microtubules are less stable.

Protein complexes show correlation with metastable distributions.

Abstract

[abridged] Background: The distribution of chemical species in an open system at metastable equilibrium can be expressed as a function of environmental variables which can include temperature, oxidation-reduction potential and others. Calculations of metastable equilibrium for various model systems were used to characterize chemical transformations among proteins and groups of proteins found in different compartments of yeast cells. Results: With increasing oxygen fugacity, the relative metastability fields of model proteins for major subcellular compartments go as mitochondrion, endoplasmic reticulum, cytoplasm, nucleus. In a metastable equilibrium setting at relatively high oxygen fugacity, proteins making up actin are predominant, but those constituting the microtubule occur with a low chemical activity. A reaction sequence involving the microtubule and spindle pole proteins was predicted by combining the known intercompartmental interactions with a hypothetical program of oxygen fugacity changes in the local environment. In further calculations, the most-abundant proteins within compartments generally occur in relative abundances that only weakly correspond to a metastable equilibrium distribution. However, physiological populations of proteins that form complexes often show an overall positive or negative correlation with the relative abundances of proteins in metastable assemblages. Conclusions: This study explored the outlines of a thermodynamic description of chemical transformations among interacting proteins in yeast cells. The results suggest that these methods can be used to measure the degree of departure of a natural biochemical process or population from a local minimum in Gibbs energy.