Modeling Hsp70-mediated protein folding.

Biophysical Journal
Bin HuMasaru Tomita

Abstract

The Hsp70 chaperone system is the major molecular chaperone system that assists protein-folding processes in all cells. To understand these processes, we analyzed the kinetic characteristics of the Escherichia coli homologs of this chaperone system during folding of a denatured protein using computer simulations and compared the results with in vitro refolding experiments. Rate constants used for the model were derived from recent literature or were determined and scrutinized for their applicability to the refolding reaction. Our simulation results are consistent with reported laboratory experiments, not only simulating the refolding reaction of wild-type proteins but also the behavior of mutant variants. Variation of kinetic parameters and concentrations of components of the Hsp70 system demonstrate the robustness of the chaperone system in assisting protein folding. Furthermore, the importance of the synergistic stimulation of the ATPase activity of Hsp70 is demonstrated. The limitations of our kinetic model indicate sore spots in our understanding of this chaperone system. Our model provides a platform for further research on chaperone action and the mechanism of chaperone-assisted refolding of denatured proteins.

References

Aug 1, 1991·Current Opinion in Cell Biology·M J Gething
Apr 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·K LiberekM Zylicz
Sep 22, 1995·The Journal of Biological Chemistry·C KingL Greene
May 26, 1995·Journal of Molecular Biology·J S McCartyB Bukau
Feb 18, 1994·Science·D SchmidP Christen
May 10, 1996·The Journal of Biological Chemistry·A W Karzai, R McMacken
Nov 15, 1996·Journal of Molecular Biology·H TheyssenJ Reinstein
Feb 26, 1998·Cell·B Bukau, A L Horwich
Apr 18, 1998·The Journal of Biological Chemistry·E V PierpaoliP Christen
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M K GreeneS J Landry
Jun 23, 1998·The Journal of Biological Chemistry·E C SchirmerS Lindquist
Jun 27, 1998·Journal of Molecular Biology·S M GislerP Christen
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·W C SuhC A Gross
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·C S GässlerB Bukau
Mar 9, 1999·Bioinformatics·M TomitaC A Hutchison
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·T LaufenB Bukau
Jul 6, 2000·Nature Structural Biology·M P MayerB Bukau
Apr 27, 2001·Nature Structural Biology·D BrehmerB Bukau
Mar 1, 2002·Advances in Protein Chemistry·M P MayerB Bukau
Apr 30, 2003·Biochemistry·Pernilla Wittung-StafshedeSamuel J Landry
Aug 28, 2003·The Journal of Biological Chemistry·Katrin LinkeUrsula Jakob
Mar 3, 2004·Bioinformatics·Kouichi TakahashiMasaru Tomita
Apr 23, 2004·The Journal of Biological Chemistry·Dirk BrehmerBernd Bukau
Oct 16, 2004·The Journal of Biological Chemistry·Jonathan J SilbergLarry E Vickery
Feb 4, 2006·Molecular Cell·Markus VogelMatthias P Mayer

❮ Previous
Next ❯

Citations

Sep 10, 2013·Trends in Biochemical Sciences·Matthias P Mayer
Oct 19, 2010·Nature Chemical Biology·Sandeep K SharmaPierre Goloubinoff
Jun 27, 2012·Molecular BioSystems·Sharan R SrinivasanJason E Gestwicki
Nov 19, 2013·PLoS Computational Biology·Alex Dickson, Charles L Brooks
Jul 6, 2014·PLoS Computational Biology·Marc GriesemerLinda Petzold
Aug 22, 2009·Chemical Biology & Drug Design·Jason CellittiMaurizio Pellecchia
Mar 5, 2011·Cell Biochemistry and Function·Thiago Gomes HeckPaulo I Homem de Bittencourt
Aug 14, 2012·Protein Science : a Publication of the Protein Society·Ashok SekharSilvia Cavagnero
Dec 18, 2012·Journal of Medical Microbiology·Sukanlaya LeejaeSupayang Piyawan Voravuthikunchai
Apr 18, 2012·Cell Reports·Evan T PowersLila M Gierasch
Apr 21, 2012·Chemistry : a European Journal·Hannah GelmanMartin Gruebele
Oct 24, 2009·Cellular and Molecular Life Sciences : CMLS·Andrew I Jewett, Joan-Emma Shea
Dec 18, 2019·ELife·Salvatore AssenzaAlessandro Barducci
Oct 27, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ke ChenBernhard O Palsson
Nov 13, 2018·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Jenny S Paul, Brian C Small
Aug 19, 2008·Archives of Biochemistry and Biophysics·Patrick G Needham, Daniel C Masison

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.