Folding and assembly of the large molecular machine Hsp90 studied in single-molecule experiments

Proceedings of the National Academy of Sciences of the United States of America
Markus JahnMatthias Rief

Abstract

Folding of small proteins often occurs in a two-state manner and is well understood both experimentally and theoretically. However, many proteins are much larger and often populate misfolded states, complicating their folding process significantly. Here we study the complete folding and assembly process of the 1,418 amino acid, dimeric chaperone Hsp90 using single-molecule optical tweezers. Although the isolated C-terminal domain shows two-state folding, we find that the isolated N-terminal as well as the middle domain populate ensembles of fast-forming, misfolded states. These intradomain misfolds slow down folding by an order of magnitude. Modeling folding as a competition between productive and misfolding pathways allows us to fully describe the folding kinetics. Beyond intradomain misfolding, folding of the full-length protein is further slowed by the formation of interdomain misfolds, suggesting that with growing chain lengths, such misfolds will dominate folding kinetics. Interestingly, we find that small stretching forces applied to the chain can accelerate folding by preventing the formation of cross-domain misfolding intermediates by leading the protein along productive pathways to the native state. The same effect is ...Continue Reading

References

Jan 1, 1997·Annual Review of Physical Chemistry·J N OnuchicP G Wolynes
Jan 31, 1998·The Journal of Biological Chemistry·A N Fedorov, T O Baldwin
Apr 30, 1999·Science·M ShtilermanS W Englander
Dec 14, 1999·Nature Structural Biology·A F OberhauserJ M Fernandez
Jul 7, 2001·The Journal of Biological Chemistry·K RichterJ Buchner
Aug 22, 2003·Protein Science : a Publication of the Protein Society·Dmitry N IvankovAlexei V Finkelstein
Aug 9, 2005·Protein Engineering, Design & Selection : PEDS·U Bastolla, Lloyd Demetrius
Apr 21, 2006·Nature·Maruf M U AliLaurence H Pearl
Jan 24, 2007·Current Opinion in Structural Biology·David J Brockwell, Sheena E Radford
Aug 21, 2007·Biophysical Journal·Michael SchlierfMatthias Rief
Jan 5, 2008·Science·William J GreenleafSteven M Block
Sep 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ying WuOsman Bilsel
Feb 24, 2009·Nature Structural & Molecular Biology·Moritz MicklerThorsten Hugel
Apr 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Thomas BornschlöglMatthias Rief
May 25, 2010·Nature·Elizabeth A ShankCarlos Bustamante
Apr 13, 2011·Proceedings of the National Academy of Sciences of the United States of America·Fei XiaFrauke Gräter
Oct 29, 2011·Science·Johannes StiglerMatthias Rief
Mar 17, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hao YuMichael T Woodside
Oct 2, 2012·The Review of Scientific Instruments·Yann von HansenRoland R Netz
Nov 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Benjamin T WaltersS Walter Englander
Aug 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Pétur O HeidarssonCiro Cecconi
Dec 4, 2014·Proceedings of the National Academy of Sciences of the United States of America·Markus JahnThorsten Hugel
Feb 18, 2015·Nature Communications·João M NunesDaniel J Müller
Sep 26, 2015·Science·Hoi Sung ChungWilliam A Eaton

❮ Previous
Next ❯

Citations

Sep 19, 2016·Journal of Molecular Biology·Jörg SchönfelderRaul Perez-Jimenez
Jul 6, 2017·Journal of the American Chemical Society·Robert WalderThomas T Perkins
Aug 3, 2017·Nanotechnology·Xiaodan ZhaoJie Yan
Oct 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Thomas SurenMatthias Rief
Jun 23, 2020·Annual Review of Biochemistry·Carlos BustamanteChristian M Kaiser
Sep 27, 2019·Scientific Reports·Marie SynakewiczLaura S Itzhaki
Apr 2, 2018·The Journal of Chemical Physics·Haim Yuval AviramGilad Haran
Jan 9, 2019·Frontiers in Molecular Neuroscience·Dhawal ChoudharyCiro Cecconi
Jan 16, 2020·Biomolecules·Marija LiutkuteMarina V Rodnina
Apr 8, 2020·Cell Stress & Chaperones·Dhawal ChoudharyCiro Cecconi
Mar 28, 2017·Protein Science : a Publication of the Protein Society·Mario J AvellanedaSander J Tans
May 26, 2016·Protein Science : a Publication of the Protein Society·Duyoung MinJames U Bowie
May 6, 2017·Protein Science : a Publication of the Protein Society·Kaixian LiuChristian M Kaiser
Nov 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Kaixian LiuChristian M Kaiser
Aug 22, 2017·Journal of Molecular Biology·Jackson C Halpin, Timothy O Street
May 15, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kevin MaciubaChristian M Kaiser
May 15, 2021·Biophysical Journal·Kevin MaciubaChristian M Kaiser
Sep 21, 2019·Journal of Chemical Theory and Computation·Ilda D'AnnessaGiorgio Colombo
Jun 21, 2016·Bioconjugate Chemistry·Ann Mukhortava, Michael Schlierf
Sep 27, 2018·Nano Letters·Weixiang YeCarsten Sönnichsen
Sep 5, 2018·The Journal of Physical Chemistry. B·Katarzyna M TychMatthias Rief
Aug 22, 2021·Journal of Molecular Biology·Rafayel PetrosyanMichael T Woodside
Sep 2, 2021·JACS Au·Fabian DingfelderBenjamin Schuler

❮ 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.