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Molecular Chaperones and Protein Folding

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.
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Molecular Chaperones and Protein Folding

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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...

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Related Experiment Video

Updated: Jan 13, 2026

Detection of the pH-dependent Activity of Escherichia coli Chaperone HdeB In Vitro and In Vivo

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Published on: October 23, 2016

Chaperone dependency during biogenesis does not correlate with chaperone dependency during refolding.

Divya Yadav¹, İdil I Demiralp^1,2, Mark Fakler¹

¹Department of Chemistry, Johns Hopkins University, Baltimore, MD, 21218, USA.

Molecular Systems Biology

|October 29, 2025

Summary

Molecular chaperones aid protein folding, but their in vivo roles differ from in vitro refolding. Deleting E. coli chaperones DnaKJ and trigger factor revealed that co-translational folding is crucial for some proteins, not just chaperone assistance.

Keywords:

Chaperones Co-translational Folding DnaK Structural Proteomics Trigger Factor

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Area of Science:

Molecular biology
Protein folding
Biochemistry

Background:

Proteins require molecular chaperones for proper folding into functional structures.
In vivo protein biogenesis roles of chaperones may differ from in vitro refolding functions.

Purpose of the Study:

To investigate the in vivo structural impact of deleting key E. coli chaperones, trigger factor and DnaKJ.
To determine if proteins unable to refold in vitro rely more on chaperones for in vivo folding.

Main Methods:

Limited proteolysis mass spectrometry (LiP-MS) was employed to analyze structural changes in the E. coli proteome.
Comparative analysis of protein structures upon deletion of trigger factor and DnaKJ chaperones.

Main Results:

DnaKJ deletion caused widespread structural changes in soluble E. coli proteins.
Trigger factor deletion affected the structures of only a limited number of proteins.
Proteins that cannot refold spontaneously or with in vitro chaperone assistance are not necessarily chaperone-dependent in vivo.

Conclusions:

Chaperone-nonrefolding proteins are likely obligate co-translational folders.
The vectorial process of co-translational folding acts as a primary "chaperone" for certain E. coli proteins.
In vivo protein folding mechanisms are complex and context-dependent.