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Updated: Jul 20, 2025

Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay
Published on: July 21, 2021
Molecular Chaperone Receptors: An Update
Thiago J Borges1, Ayesha Murshid2, Jimmy Theriault2
1Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Abstract:
Extracellular heat shock proteins (HSP) play important roles in cell signaling and immunity. Many of these effects are mediated by surface receptors expressed on a wide range of cell types, including immune cells. We have investigated the nature of such proteins by cloning candidate receptors into cells (CHO-K1) with the rare property of being null for HSP binding. Using this approach, we have discovered that mammalian and eukaryotic Hsp70 binds avidly to at least three classes of receptor including: (1) c-type lectin receptors (CLR), (2) scavenger receptors (SR) and (3) lectins. However, the structural nature of the receptor-ligand interactions is not currently clear. Hsp70 can bind to LOX-1 (a member of both the CLR and SR), with the c-type lectin binding domain (CTLD), to the SR family members SREC-I and FEEL-1/CLEVER-1/STABILIN-1, which by contrast have arrays of EGF-like repeats in their extracellular domains as well. In this chapter, we will discuss: (1) methods for the discovery of HSP receptors, (2) approaches to the study of individual receptors in cells that contain multiple such receptors and (3) methods for investigating HSP receptor function in vivo.
Insights
Extracellular heat shock proteins (HSP) bind to immune cell receptors. This study identifies c-type lectin receptors, scavenger receptors, and lectins as key binding partners for Hsp70, advancing our understanding of HSP-mediated signaling.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Extracellular heat shock proteins (HSP) are crucial for cell signaling and immune responses.
- Surface receptors on immune cells mediate many HSP effects.
- Understanding these receptor-ligand interactions is key to deciphering HSP functions.
Purpose of the Study:
- To identify and characterize receptors that bind extracellular heat shock proteins (HSP).
- To investigate the structural basis of Hsp70 interactions with its receptors.
- To outline methods for discovering and studying HSP receptors and their functions.
Main Methods:
- Cloning candidate receptors into HSP-binding null cells (CHO-K1).
- Investigating binding of mammalian and eukaryotic Hsp70 to various receptor classes.
- Analyzing receptor domains involved in Hsp70 binding, including CTLD and EGF-like repeats.
Main Results:
- Hsp70 avidly binds to at least three receptor classes: c-type lectin receptors (CLR), scavenger receptors (SR), and lectins.
- Hsp70 interacts with LOX-1 via its c-type lectin binding domain (CTLD).
- Hsp70 also binds to SR family members SREC-I and FEEL-1/CLEVER-1/STABILIN-1, which possess EGF-like repeats.
Conclusions:
- Identified CLR, SR, and lectins as major classes of Hsp70 receptors.
- Provided insights into specific receptor-ligand interactions, such as Hsp70 with LOX-1.
- Established a framework for discovering and studying HSP receptors and their in vivo functions.
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