Different conformations for the same polypeptide bound to chaperones DnaK and GroEL.

Area of Science:

• Molecular biology
• Structural biology
• Biochemistry

Background:

• DnaK (hsp70) and GroEL (cpn60) are essential molecular chaperones in E. coli, representing conserved protein families.
• Molecular chaperones play critical roles in protein folding, stability, and cellular function.
• Understanding chaperone-client interactions at a molecular level is key to deciphering cellular processes.

Purpose of the Study:

• To investigate the conformational states of a model peptide (vsv-C) when bound to two distinct molecular chaperones, DnaK and GroEL.
• To elucidate the impact of chaperone binding on peptide backbone and side-chain mobility.

Main Methods:

• Utilized transferred nuclear Overhauser effects (tr-NOE) in two-dimensional NMR spectroscopy.
• Analyzed the vsv-C peptide (KLIGVLSSLFRPK) in complex with DnaK and GroEL.

Main Results:

• The vsv-C peptide adopts an extended conformation when bound to DnaK.
• The vsv-C peptide adopts a helical conformation when bound to GroEL.
• Peptide backbone mobility is significantly reduced upon binding to DnaK compared to GroEL.
• Side-chain mobility is more restricted when the peptide is bound to GroEL than to DnaK.

Conclusions:

• DnaK and GroEL induce distinct conformational changes in bound peptides.
• Chaperone-induced conformational preferences influence the dynamics of peptide segments differently.
• These findings provide insights into the mechanisms by which molecular chaperones recognize and process substrate proteins.