Evaluating Effects of Cellular Environment on Protein Folding

Abstract

Protein structures are fundamental to their functions and interactions, requiring extensive investigation in structural proteomics. The cellular environment, including factors such as temperature, pH, and salinity, has been shown to have a profound impact on protein folding. Despite the significance of these factors, they are frequently overlooked by protein structure models and studies. This Thesis is a collection of publications that offer insight into the complex interactions between cellular environment and protein folding dynamics.

The first publication focuses on differences in protein folding between mesophilic and thermophilic bacteria. We uncover distinctions in secondary structure when using mesophiles as expression systems for thermophiles. Understanding these variations may aid in bacterial physiology comprehension and refinement of protein structure prediction models to better account for environmental influences.

The second publication explores the relationship between amino acid sequence similarities and secondary structure variations in mammalian ACE2 proteins. Given the critical role of ACE2 in mediating coronavirus cellular entry, understanding the structural determinants governing ACE2 binding interactions is crucial. Our findings offer insights into the molecular mechanisms underlying virus-host interactions, providing additional context for therapeutic and vaccine development efforts.

The third publication investigates intrinsically disordered protein (IDP) abundance across bacteria with varying optimal growth temperatures (OGTs). IDPs play versatile roles in cellular processes, with their abundance linked to environmental adaptation. Comparing IDP abundance in mesophilic and thermophilic bacteria sheds light on potential functional implications in diverse environmental contexts. This analysis enhances our understanding of protein dynamics in response to environmental cues and provides insights into bacterial adaptation and evolution.

Through these investigations, we contribute to bridging knowledge gaps regarding the influence of cellular environment on protein folding dynamics. By unraveling the complex interplay between environmental factors and protein structure, we pave the way for more accurate predictions and manipulations of protein function.