Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine.

Nature Structural & Molecular Biology
Steven E GlynnRobert T Sauer

Abstract

In the Escherichia coli ClpXP protease, a hexameric ClpX ring couples ATP binding and hydrolysis to mechanical protein unfolding and translocation into the ClpP degradation chamber. Rigid-body packing between the small AAA+ domain of each ClpX subunit and the large AAA+ domain of its neighbor stabilizes the hexamer. By connecting the parts of each rigid-body unit with disulfide bonds or linkers, we created covalently closed rings that retained robust activity. A single-residue insertion in the hinge that connects the large and small AAA+ domains and forms part of the nucleotide-binding site uncoupled ATP hydrolysis from productive unfolding. We propose that ATP hydrolysis drives changes in the conformation of one hinge and its flanking domains and that the changes are propagated around the AAA+ ring through the topologically constrained set of rigid-body units and hinges to produce coupled ring motions that power substrate unfolding.

References

Jan 1, 1988·Methods in Enzymology·J G Nørby
Sep 29, 2000·Science·I LevchenkoT A Baker
Aug 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Joel R HoskinsSue Wickner
Sep 3, 2002·The Journal of Biological Chemistry·Fusheng GuoDi Xia
Sep 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ryoko AndoAtsushi Miyawaki
Aug 26, 2003·The Journal of Biological Chemistry·Urszula A WojtyraWalid A Houry
Sep 30, 2003·The Journal of Biological Chemistry·Dong Young Kim, Kyeong Kyu Kim
Mar 24, 2004·Journal of Structural Biology·Joaquin OrtegaAlasdair C Steven
Apr 6, 2004·Nature Structural & Molecular Biology·Shilpa A JoshiRobert T Sauer
Jun 3, 2004·Genome Research·Gavin E CrooksSteven E Brenner
Jan 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jon A KennistonRobert T Sauer
Aug 3, 2005·Nature Reviews. Molecular Cell Biology·Phyllis I Hanson, Sidney W Whiteheart
Oct 21, 2005·Nature·Andreas MartinRobert T Sauer
Jul 11, 2006·Nature Structural & Molecular Biology·Jan P ErzbergerJames M Berger
Sep 28, 2007·Traffic·Susan Roehl White, Brett Lauring
Jan 29, 2008·Nature Structural & Molecular Biology·Andreas MartinRobert T Sauer
Oct 22, 2008·Nature Structural & Molecular Biology·Andreas MartinRobert T Sauer
Jul 6, 2010·Journal of Molecular Biology·Ramona E Duman, Jan Löwe
Jul 9, 2011·Biochimica Et Biophysica Acta·Tania A Baker, Robert T Sauer
Aug 9, 2011·Journal of Molecular Biology·Andrew R NagerRobert T Sauer

❮ Previous
Next ❯

Citations

Jun 19, 2013·Nature Structural & Molecular Biology·Mary E MatyskielaAndreas Martin
Sep 10, 2013·Nature Structural & Molecular Biology·Robyn BeckwithAndreas Martin
Apr 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Paweł ŚledźWolfgang Baumeister
Feb 18, 2014·Acta Crystallographica. Section D, Biological Crystallography·Cathleen ZeymerJochen Reinstein
Dec 10, 2013·Trends in Biochemical Sciences·Kristofor Nyquist, Andreas Martin
Jun 5, 2014·Annual Review of Biophysics·Carlos J BustamanteChristian A M Wilson
Apr 9, 2014·Proceedings of the National Academy of Sciences of the United States of America·Dominik BarthelmeRobert T Sauer
Mar 26, 2013·Cellular and Molecular Bioengineering·Wonmuk Hwang, Matthew J Lang
Dec 3, 2013·FEBS Letters·Alan A DombkowskiDouglas B Craig
Jul 3, 2015·Protein Science : a Publication of the Protein Society·Dominik BarthelmeRobert T Sauer
Nov 25, 2014·Cell·Gira BhabhaRonald D Vale
Aug 22, 2013·Protein Science : a Publication of the Protein Society·Robert T Sauer
Nov 14, 2012·Journal of Molecular Biology·Mary E Matyskiela, Andreas Martin
Feb 19, 2013·Journal of Molecular Biology·Paweł SledźWolfgang Baumeister
Sep 10, 2013·Structure·Friedrich FörsterWolfgang Baumeister
Jan 20, 2015·Nature Chemical Biology·Ohad IosefsonRobert T Sauer
May 14, 2016·ACS Chemical Biology·Tengfeng NiCai-Guang Yang
Sep 28, 2016·Cellular and Molecular Life Sciences : CMLS·Tatyana A Sysoeva
Nov 1, 2016·Nature Structural & Molecular Biology·Piere Rodriguez-AliagaAndreas Martin
Apr 14, 2018·Annual Review of Biochemistry·Jared A M BardAndreas Martin
Dec 8, 2015·Nature Reviews. Microbiology·Adrian O OlivaresRobert T Sauer
Jan 24, 2014·Nature Reviews. Molecular Cell Biology·Sucharita BhattacharyyaAndreas Matouschek
Mar 15, 2016·Biopolymers·Lisa-Marie BittnerFranz Narberhaus
Feb 13, 2018·Annual Review of Physiology·Adrian O OlivaresRobert T Sauer
Mar 27, 2013·The Journal of Biological Chemistry·Priscilla Hiu-Mei TooPhilip Coffino
Nov 11, 2016·Molecular BioSystems·Fei YeCai-Guang Yang
Mar 4, 2020·Scientific Reports·Venkata Raveendra PothineniJayakumar Rajadas
Nov 23, 2018·International Journal of Molecular Sciences·Justin D MarseeJustin M Miller

❮ Previous
Next ❯

Methods Mentioned

BETA
gel-filtration

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.