Escorts take the lead molecular chaperones as therapeutic targets

Dumaine Williams1, Lakshmi A Devi

  • 1Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, USA.

Insights

Molecular chaperones regulate the function and trafficking of seven-transmembrane-containing G-protein-coupled receptors. Understanding these chaperones offers potential new therapeutic targets for diseases linked to receptor dysfunction.

Area of Science:

  • Molecular biology
  • Cellular physiology
  • Pharmacology

Background:

  • Transmembrane receptors exhibit diverse functions influenced by pharmacology, signaling, and trafficking.
  • Receptor mutations can cause misfolding, intracellular retention, and impaired signaling, leading to various diseases.
  • Ineffective receptor signaling due to intracellular retention is a significant factor in disease pathogenesis.

Purpose of the Study:

  • To discuss the role of molecular chaperones in regulating the function and trafficking of G-protein-coupled receptors (GPCRs).
  • To explore the potential of molecular chaperones as therapeutic targets for diseases associated with GPCR dysfunction.
  • To elucidate how chaperones influence receptor maturation, sorting, and cell surface expression.

Main Methods:

  • Review of existing literature on molecular chaperones and G-protein-coupled receptor biology.
  • Analysis of studies investigating receptor trafficking and cell surface expression.
  • Exploration of the regulatory mechanisms of chaperones in GPCRs.

Main Results:

  • Molecular chaperones are identified as critical regulators of receptor maturation and sorting.
  • Chaperones play a key role in controlling the trafficking and cell surface expression of seven-transmembrane receptors.
  • Dysfunctional receptor trafficking, influenced by chaperones, is linked to various diseases.

Conclusions:

  • Molecular chaperones are essential for proper G-protein-coupled receptor function and trafficking.
  • Targeting molecular chaperones presents a promising strategy for developing novel therapeutics.
  • Further research into chaperone-GPCR interactions can illuminate disease mechanisms and treatment opportunities.

Related Concept Videos

Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
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...
DNA Helicases00:55

DNA Helicases

DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...