Using Single-Molecule Approaches to Understand the Molecular Mechanisms of Heat-Shock Protein Chaperone Function

Abstract

The heat-shock proteins (Hsp) are a family of molecular chaperones, which collectively form a network that is critical for the maintenance of protein homeostasis. Traditional ensemble-based measurements have provided a wealth of knowledge on the function of individual Hsps and the Hsp network; however, such techniques are limited in their ability to resolve the heterogeneous, dynamic and transient interactions that molecular chaperones make with their client proteins. Single-molecule techniques have emerged as a powerful tool to study dynamic biological systems, as they enable rare and transient populations to be identified that would usually be masked in ensemble measurements. Thus, single-molecule techniques are particularly amenable for the study of Hsps and have begun to be used to reveal novel mechanistic details of their function. In this review, we discuss the current understanding of the chaperone action of Hsps and how gaps in the field can be addressed using single-molecule methods. Specifically, this review focuses on the ATP-independent small Hsps and the broader Hsp network and describes how these dynamic systems are amenable to single-molecule techniques.

Heat Shock Protein 40 (HSP40) in Pacific White Shrimp (Litopenaeus vannamei): Molecular Cloning, Tissue Distribution and Ontogeny, Response to Temperature, Acidity/Alkalinity and Salinity Stresses, and Potential Role in Ovarian Development

“…Heat shock proteins (HSPs), also known as heat stress proteins, are a family of proteins that are produced by cells in response to various stressful conditions (Zhu et al, 1996; Johnston et al, 2018). HSPs were first identified in fruit flies that were exposed to a severely heat-shocked environment (Ritossa, 1962) and were subsequently demonstrated to be ubiquitously and evolutionarily conserved molecular chaperones that are present in all living organisms (Srivastava, 2002).…”

“…Moreover, HSPs may perform a multitude of housekeeping functions that are essential for cell survival (Srivastava, 2002). Under normal conditions, HSPs participate in cellular processes such as protein folding and transport, cell cycle regulation and apoptosis (Mallouk et al, 1999; Johnston et al, 2018), as well as in physiological processes such as embryonic development, gonadal development and spermatogenesis (Allen et al, 1996; Binder, 2014; Chan et al, 2014).…”

Analysis of the transcriptome data in Litopenaeus vannamei reveals the immune basis and predicts the hub regulation-genes in response to high-pH stress

“…Heat shock proteins (HSPs) are defined as molecular chaperones, which play vital roles in maintaining protein homeostasis and in facilitating protein folding and degradation [122]. According to their monomeric molecular mass, HSPs are divided into HSP100, HSP90, HSP70, HSP60, HSP40 and small HSPs (sHSPs) [81, 122]. HSP70s are implicated in a wide variety of cellular processes via binding their substrate-binding domain to a short polypeptide with recognition motifs [123].…”

Do Alarmins Have a Potential Role in Autism Spectrum Disorders Pathogenesis and Progression?

“…The heat-shock proteins (Hsp) represent a group of molecular chaperones, fundamental for the maintenance of protein homeostasis [54]. In human beings, 332 genes encode for the chaperone and co-chaperone families, and together constitute the “chaperome” [55].…”