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Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate.

Fei X, Bell TA, Jenni S, Stinson BM, Baker TA, Harrison SC, Sauer RT.

Elife. 2020 Feb 28;9. pii: e52774. doi: 10.7554/eLife.52774.


The Non-dominant AAA+ Ring in the ClpAP Protease Functions as an Anti-stalling Motor to Accelerate Protein Unfolding and Translocation.

Kotamarthi HC, Sauer RT, Baker TA.

Cell Rep. 2020 Feb 25;30(8):2644-2654.e3. doi: 10.1016/j.celrep.2020.01.110.


Acyldepsipeptide Antibiotics and a Bioactive Fragment Thereof Differentially Perturb Mycobacterium tuberculosis ClpXP1P2 Activity in vitro.

Schmitz KR, Handy EL, Compton CL, Gupta S, Bishai WR, Sauer RT, Sello JK.

ACS Chem Biol. 2020 Feb 21. doi: 10.1021/acschembio.9b00454. [Epub ahead of print]


Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding.

Bell TA, Baker TA, Sauer RT.

Elife. 2019 Jun 28;8. pii: e46808. doi: 10.7554/eLife.46808.


Roles of the ClpX IGF loops in ClpP association, dissociation, and protein degradation.

Amor AJ, Schmitz KR, Baker TA, Sauer RT.

Protein Sci. 2019 Apr;28(4):756-765. doi: 10.1002/pro.3590. Epub 2019 Mar 4.


A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites.

Tang Y, Meister TR, Walczak M, Pulkoski-Gross MJ, Hari SB, Sauer RT, Amberg-Johnson K, Yeh E.

PLoS Biol. 2019 Feb 6;17(2):e3000136. doi: 10.1371/journal.pbio.3000136. eCollection 2019 Feb.


Hinge-Linker Elements in the AAA+ Protein Unfoldase ClpX Mediate Intersubunit Communication, Assembly, and Mechanical Activity.

Bell TA, Baker TA, Sauer RT.

Biochemistry. 2018 Dec 11;57(49):6787-6796. doi: 10.1021/acs.biochem.8b00907. Epub 2018 Nov 20.


Structural and Functional Analysis of E. coli Cyclopropane Fatty Acid Synthase.

Hari SB, Grant RA, Sauer RT.

Structure. 2018 Sep 4;26(9):1251-1258.e3. doi: 10.1016/j.str.2018.06.008. Epub 2018 Jul 26.


Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme.

Brown BL, Kardon JR, Sauer RT, Baker TA.

Structure. 2018 Apr 3;26(4):580-589.e4. doi: 10.1016/j.str.2018.02.012. Epub 2018 Mar 15.


Mechanical Protein Unfolding and Degradation.

Olivares AO, Baker TA, Sauer RT.

Annu Rev Physiol. 2018 Feb 10;80:413-429. doi: 10.1146/annurev-physiol-021317-121303. Review.


Small molecule inhibition of apicomplexan FtsH1 disrupts plastid biogenesis in human pathogens.

Amberg-Johnson K, Hari SB, Ganesan SM, Lorenzi HA, Sauer RT, Niles JC, Yeh E.

Elife. 2017 Aug 18;6. pii: e29865. doi: 10.7554/eLife.29865.


Effect of directional pulling on mechanical protein degradation by ATP-dependent proteolytic machines.

Olivares AO, Kotamarthi HC, Stein BJ, Sauer RT, Baker TA.

Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):E6306-E6313. doi: 10.1073/pnas.1707794114. Epub 2017 Jul 19.


Covalently linked HslU hexamers support a probabilistic mechanism that links ATP hydrolysis to protein unfolding and translocation.

Baytshtok V, Chen J, Glynn SE, Nager AR, Grant RA, Baker TA, Sauer RT.

J Biol Chem. 2017 Apr 7;292(14):5695-5704. doi: 10.1074/jbc.M116.768978. Epub 2017 Feb 21.


Rational Design of Selective and Bioactive Inhibitors of the Mycobacterium tuberculosis Proteasome.

Totaro KA, Barthelme D, Simpson PT, Jiang X, Lin G, Nathan CF, Sauer RT, Sello JK.

ACS Infect Dis. 2017 Feb 10;3(2):176-181. doi: 10.1021/acsinfecdis.6b00172. Epub 2016 Dec 5.


The AAA+ FtsH Protease Degrades an ssrA-Tagged Model Protein in the Inner Membrane of Escherichia coli.

Hari SB, Sauer RT.

Biochemistry. 2016 Oct 11;55(40):5649-5652. Epub 2016 Sep 30.


A Structurally Dynamic Region of the HslU Intermediate Domain Controls Protein Degradation and ATP Hydrolysis.

Baytshtok V, Fei X, Grant RA, Baker TA, Sauer RT.

Structure. 2016 Oct 4;24(10):1766-1777. doi: 10.1016/j.str.2016.08.012. Epub 2016 Sep 22.


Highly Dynamic Interactions Maintain Kinetic Stability of the ClpXP Protease During the ATP-Fueled Mechanical Cycle.

Amor AJ, Schmitz KR, Sello JK, Baker TA, Sauer RT.

ACS Chem Biol. 2016 Jun 17;11(6):1552-1560. doi: 10.1021/acschembio.6b00083. Epub 2016 Mar 30.


Structural Basis of an N-Degron Adaptor with More Stringent Specificity.

Stein BJ, Grant RA, Sauer RT, Baker TA.

Structure. 2016 Feb 2;24(2):232-42. doi: 10.1016/j.str.2015.12.008. Epub 2016 Jan 21.


Mechanistic insights into bacterial AAA+ proteases and protein-remodelling machines.

Olivares AO, Baker TA, Sauer RT.

Nat Rev Microbiol. 2016 Jan;14(1):33-44. doi: 10.1038/nrmicro.2015.4. Epub 2015 Dec 7. Review.


Origin and Functional Evolution of the Cdc48/p97/VCP AAA+ Protein Unfolding and Remodeling Machine.

Barthelme D, Sauer RT.

J Mol Biol. 2016 May 8;428(9 Pt B):1861-9. doi: 10.1016/j.jmb.2015.11.015. Epub 2015 Dec 1. Review.


Substrate-guided optimization of the syringolins yields potent proteasome inhibitors with activity against leukemia cell lines.

Totaro KA, Barthelme D, Simpson PT, Sauer RT, Sello JK.

Bioorg Med Chem. 2015 Sep 15;23(18):6218-22. doi: 10.1016/j.bmc.2015.07.041. Epub 2015 Jul 26.


Dissection of Axial-Pore Loop Function during Unfolding and Translocation by a AAA+ Proteolytic Machine.

Iosefson O, Olivares AO, Baker TA, Sauer RT.

Cell Rep. 2015 Aug 11;12(6):1032-41. doi: 10.1016/j.celrep.2015.07.007. Epub 2015 Jul 30.


Examination of a Structural Model of Peptidomimicry by Cyclic Acyldepsipeptide Antibiotics in Their Interaction with the ClpP Peptidase.

Carney DW, Schmitz KR, Scruse AC, Sauer RT, Sello JK.

Chembiochem. 2015 Sep 7;16(13):1875-1879. doi: 10.1002/cbic.201500234. Epub 2015 Jul 27.


An ALS disease mutation in Cdc48/p97 impairs 20S proteasome binding and proteolytic communication.

Barthelme D, Jauregui R, Sauer RT.

Protein Sci. 2015 Sep;24(9):1521-7. doi: 10.1002/pro.2740. Epub 2015 Jul 14.


Assaying the kinetics of protein denaturation catalyzed by AAA+ unfolding machines and proteases.

Baytshtok V, Baker TA, Sauer RT.

Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5377-82. doi: 10.1073/pnas.1505881112. Epub 2015 Apr 13.


Subunit asymmetry and roles of conformational switching in the hexameric AAA+ ring of ClpX.

Stinson BM, Baytshtok V, Schmitz KR, Baker TA, Sauer RT.

Nat Struct Mol Biol. 2015 May;22(5):411-6. doi: 10.1038/nsmb.3012. Epub 2015 Apr 13.


Deciphering the Roles of Multicomponent Recognition Signals by the AAA+ Unfoldase ClpX.

Ling L, Montaño SP, Sauer RT, Rice PA, Baker TA.

J Mol Biol. 2015 Sep 11;427(18):2966-82. doi: 10.1016/j.jmb.2015.03.008. Epub 2015 Mar 19.


Erratum: Coordinated gripping of substrate by subunits of an AAA+ proteolytic machine.

Iosefson O, Nager AR, Baker TA, Sauer RT.

Nat Chem Biol. 2015 Apr;11(4):299. doi: 10.1038/nchembio0415-299a. No abstract available.


Steric clashes with bound OMP peptides activate the DegS stress-response protease.

de Regt AK, Baker TA, Sauer RT.

Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3326-31. doi: 10.1073/pnas.1502372112. Epub 2015 Mar 2.


A conserved activation cluster is required for allosteric communication in HtrA-family proteases.

de Regt AK, Kim S, Sohn J, Grant RA, Baker TA, Sauer RT.

Structure. 2015 Mar 3;23(3):517-526. doi: 10.1016/j.str.2015.01.012. Epub 2015 Feb 19.


Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine.

Iosefson O, Nager AR, Baker TA, Sauer RT.

Nat Chem Biol. 2015 Mar;11(3):201-6. doi: 10.1038/nchembio.1732. Epub 2015 Jan 19. Erratum in: Nat Chem Biol. 2015 Apr;11(4):299.


Crystal structure of Mycobacterium tuberculosis ClpP1P2 suggests a model for peptidase activation by AAA+ partner binding and substrate delivery.

Schmitz KR, Carney DW, Sello JK, Sauer RT.

Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):E4587-95. doi: 10.1073/pnas.1417120111. Epub 2014 Sep 29.


A simple fragment of cyclic acyldepsipeptides is necessary and sufficient for ClpP activation and antibacterial activity.

Carney DW, Compton CL, Schmitz KR, Stevens JP, Sauer RT, Sello JK.

Chembiochem. 2014 Oct 13;15(15):2216-20. doi: 10.1002/cbic.201402358. Epub 2014 Sep 11.


Mechanochemical basis of protein degradation by a double-ring AAA+ machine.

Olivares AO, Nager AR, Iosefson O, Sauer RT, Baker TA.

Nat Struct Mol Biol. 2014 Oct;21(10):871-5. doi: 10.1038/nsmb.2885. Epub 2014 Sep 7.


Remodeling of a delivery complex allows ClpS-mediated degradation of N-degron substrates.

Rivera-Rivera I, Román-Hernández G, Sauer RT, Baker TA.

Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):E3853-9. doi: 10.1073/pnas.1414933111. Epub 2014 Sep 3.


Stochastic but highly coordinated protein unfolding and translocation by the ClpXP proteolytic machine.

Cordova JC, Olivares AO, Shin Y, Stinson BM, Calmat S, Schmitz KR, Aubin-Tam ME, Baker TA, Lang MJ, Sauer RT.

Cell. 2014 Jul 31;158(3):647-58. doi: 10.1016/j.cell.2014.05.043.


Substrate delivery by the AAA+ ClpX and ClpC1 unfoldases activates the mycobacterial ClpP1P2 peptidase.

Schmitz KR, Sauer RT.

Mol Microbiol. 2014 Aug;93(4):617-28. doi: 10.1111/mmi.12694. Epub 2014 Jul 13.


Overexpression of CupB5 activates alginate overproduction in Pseudomonas aeruginosa by a novel AlgW-dependent mechanism.

de Regt AK, Yin Y, Withers TR, Wang X, Baker TA, Sauer RT, Yu HD.

Mol Microbiol. 2014 Aug;93(3):415-25. doi: 10.1111/mmi.12665. Epub 2014 Jul 6.


Distinct regulatory mechanisms balance DegP proteolysis to maintain cellular fitness during heat stress.

Kim S, Sauer RT.

Genes Dev. 2014 Apr 15;28(8):902-11. doi: 10.1101/gad.238394.114.


Architecture and assembly of the archaeal Cdc48*20S proteasome.

Barthelme D, Chen JZ, Grabenstatter J, Baker TA, Sauer RT.

Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):E1687-94. doi: 10.1073/pnas.1404823111. Epub 2014 Apr 7.


Restriction of the conformational dynamics of the cyclic acyldepsipeptide antibiotics improves their antibacterial activity.

Carney DW, Schmitz KR, Truong JV, Sauer RT, Sello JK.

J Am Chem Soc. 2014 Feb 5;136(5):1922-9. doi: 10.1021/ja410385c. Epub 2014 Jan 24.


Roles of the N domain of the AAA+ Lon protease in substrate recognition, allosteric regulation and chaperone activity.

Wohlever ML, Baker TA, Sauer RT.

Mol Microbiol. 2014 Jan;91(1):66-78. doi: 10.1111/mmi.12444. Epub 2013 Nov 10.


A mutation in the N domain of Escherichia coli lon stabilizes dodecamers and selectively alters degradation of model substrates.

Wohlever ML, Baker TA, Sauer RT.

J Bacteriol. 2013 Dec;195(24):5622-8. doi: 10.1128/JB.00886-13. Epub 2013 Oct 11.


Antibacterial activity of and resistance to small molecule inhibitors of the ClpP peptidase.

Compton CL, Schmitz KR, Sauer RT, Sello JK.

ACS Chem Biol. 2013 Dec 20;8(12):2669-77. doi: 10.1021/cb400577b. Epub 2013 Oct 4.


Mutagenic dissection of the sequence determinants of protein folding, recognition, and machine function.

Sauer RT.

Protein Sci. 2013 Nov;22(11):1675-87. doi: 10.1002/pro.2334. Epub 2013 Sep 18.


Dual molecular signals mediate the bacterial response to outer-membrane stress.

Lima S, Guo MS, Chaba R, Gross CA, Sauer RT.

Science. 2013 May 17;340(6134):837-41. doi: 10.1126/science.1235358.


Distinct quaternary structures of the AAA+ Lon protease control substrate degradation.

Vieux EF, Wohlever ML, Chen JZ, Sauer RT, Baker TA.

Proc Natl Acad Sci U S A. 2013 May 28;110(22):E2002-8. doi: 10.1073/pnas.1307066110. Epub 2013 May 14.


Nucleotide binding and conformational switching in the hexameric ring of a AAA+ machine.

Stinson BM, Nager AR, Glynn SE, Schmitz KR, Baker TA, Sauer RT.

Cell. 2013 Apr 25;153(3):628-39. doi: 10.1016/j.cell.2013.03.029.


Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase.

Barthelme D, Sauer RT.

Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3327-32. doi: 10.1073/pnas.1300408110. Epub 2013 Feb 11.


Engineering fluorescent protein substrates for the AAA+ Lon protease.

Wohlever ML, Nager AR, Baker TA, Sauer RT.

Protein Eng Des Sel. 2013 Apr;26(4):299-305. doi: 10.1093/protein/gzs105. Epub 2013 Jan 28.

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