Role of Hsp70 in Post-Translational Protein Targeting: Tail-Anchored Membrane Proteins and Beyond

Abstract

The Hsp70 family of molecular chaperones acts as a central ‘hub’ in the cell that interacts with numerous newly synthesized proteins to assist in their biogenesis. Apart from its central and well-established role in facilitating protein folding, Hsp70s also act as key decision points in the cellular chaperone network that direct client proteins to distinct biogenesis and quality control pathways. In this paper, we review accumulating data that illustrate a new branch in the Hsp70 network: the post-translational targeting of nascent membrane and organellar proteins to diverse cellular organelles. Work in multiple pathways suggests that Hsp70, via its ability to interact with components of protein targeting and translocation machineries, can initiate elaborate substrate relays in a sophisticated cascade of chaperones, cochaperones, and receptor proteins, and thus provide a mechanism to safeguard and deliver nascent membrane proteins to the correct cellular membrane. We discuss the mechanistic principles gleaned from better-studied Hsp70-dependent targeting pathways and outline the observations and outstanding questions in less well-studied systems.

Ab initio protein structure prediction: the necessary presence of external force field as it is delivered by Hsp40 chaperone

“…Hsp70 is also interpreted as the tool delivering nascent membrane proteins of appropriate structure for that environemnt [ 65 ].…”

Unraveling the Molecular Links between Benzopyrene Exposure, NASH, and HCC: An Integrated Bioinformatics and Experimental Study

“…These proteins are crucial in cellular stress responses, playing diverse roles in maintaining cellular homeostasis and ensuring cell survival under adverse conditions 14 . HSPA1A is involved in various cellular processes, including protein folding, protein tra cking, and protection against protein aggregation 15,16 . It also participates in DNA repair mechanisms, maintaining genomic stability and integrity [17][18][19] .…”

Exploration of the truncated cytosolic Hsp70 in plants - unveiling the diverse T1 lineage and the conserved T2 lineage

“…It is worth mentioning that cyHsp70T has been reported to function as a pivotal translocation motor during the posttranslational import of cytoplasmic proteins into the endoplasmic reticulum (ER), mitochondria, and chloroplasts ( De Los Rios et al., 2006 ; Craig, 2018 ; Shan, 2023 ). Yeast Ssa1 and Ssb1 interact with the TPR motif of Sec72 to facilitate protein translocation to the ER ( Tripathi et al., 2017 ; Graham et al., 2019 ).…”