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.

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.

Related Concept Videos

Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

13.1K
Bacterial Protein Maturation01:26

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
36
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
2.6K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
6.9K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K