Folding properties of the nucleotide exchange factor GrpE from Thermus thermophilus: GrpE is a thermosensor that mediates heat shock response.


Hsp70 proteins like DnaK bind unfolded polypeptides in a nucleotide-dependent manner. The switch from high-affinity ADP-state to low- affinity ATP-state with concomitant substrate release is accelerated significantly by GrpE proteins. GrpE thus fulfils an important role in regulation of the chaperone cycle. Here, we analysed the thermal stability of GrpE from Thermus thermophilus using differential scanning calorimetry and CD-spectroscopy. The protein exhibits unusual unfolding characteristics with two observable thermal transitions. The first transition is CD-spectroscopically silent with a transition midpoint at 90 degrees C. The second transition, mainly constituting the CD-signal, ranges between 100 and 105 degrees C depending on the GrpE(Tth) concentration, according to the model N(2) <==> I(2) <==> 2U. Using a C-terminally truncated version of GrpE(Tth) it was possible to assign the second thermal transition to the dimerisation of GrpE(Tth), while the first transition represents the completely reversible unfolding of the globular C-terminal domain. The unfolding of this domain is accompanied by a distinct decrease in nucleotide exchange rates and impaired binding to DnaK(Tth). Under heat shock conditions, the DnaK-ADP-protein-substrate complex is thus stabilised by a reversibly inactivated GrpE-protein that refolds under permissive conditions. In combination with studies on GrpE from Escherichia coli presented recently by Christen and co-workers, it thus appears that the general role of GrpE is to function as a thermosensor that modulates nucleotide exchange rates in a temperature-dependent manner to prevent substrate dissociation at non-permissive conditions. Study holds ProTherm entries: 12765, 12766 Extra Details: chaperones; DnaK; GrpE; nucleotide exchange

Submission Details

ID: tWs2qTAV

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:44 p.m.

Version: 1

Publication Details
Groemping Y;Reinstein J,J. Mol. Biol. (2001) Folding properties of the nucleotide exchange factor GrpE from Thermus thermophilus: GrpE is a thermosensor that mediates heat shock response. PMID:11724541
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
3A6M 2009-09-03T00:00:00+0000 3.23 Crystal structure of GrpE from Thermus thermophilus HB8

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
99.4 Protein GrpE Q72IK6 GRPE_THET2
100.0 Protein GrpE Q56236 GRPE_THET8