Structure and function of ClpXP, a AAA+ proteolytic machine powered by probabilistic ATP hydrolysis

References

• Amor AJ, Schmitz KR, Baker TA, Sauer RT. 2019. Roles of the ClpX IGF loops in ClpP association, dissociation, and protein degradation. Protein Sci. 28(4):756–765.
   PubMed Web of Science ®Google Scholar
• Amor AJ, Schmitz KR, Sello JK, Baker TA, Sauer RT. 2016. Highly dynamic interactions maintain kinetic stability of the ClpXP protease during the ATP-fueled mechanical cycle. ACS Chem Biol. 11(6):1552–1560.
   PubMed Web of Science ®Google Scholar
• Aubin-Tam ME, Olivares AO, Sauer RT, Baker TA, Lang MJ. 2011. Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine. Cell. 145(2):257–267.
   PubMed Web of Science ®Google Scholar
• Baker TA, Sauer RT. 2006. ATP-dependent proteases of bacteria: recognition logic and operating principles. Trends Biochem Sci. 31(12):647–653.
   PubMed Web of Science ®Google Scholar
• Baker TA, Sauer RT. 2012. ClpXP, an ATP-powered unfolding and protein-degradation machine. Biochim Biophys Acta. 1823(1):15–28.
   PubMed Web of Science ®Google Scholar
• Bard JAM, Goodall EA, Greene ER, Jonsson E, Dong KC, Martin A. 2018. Structure and function of the 26S proteasome. Annu Rev Biochem. 87:697–724.
   PubMed Web of Science ®Google Scholar
• Barkow SR, Levchenko I, Baker TA, Sauer RT. 2009. Polypeptide translocation by the AAA+ ClpXP protease machine. Chem Biol. 16(6):605–612.
   PubMedGoogle Scholar
• Bell TA. 2020. Intersubunit communication and coordinated mechanical activity in the AAA+ protease ClpXP [PhD thesis]. Massachusetts Institute of Technology, Cambridge, MA.
   Google Scholar
• Bell TA, Baker TA, Sauer RT. 2018. Hinge-linker elements in the AAA+ protein unfoldase ClpX mediate intersubunit communication, assembly, and mechanical activity. Biochemistry. 57(49):6787–6796.
   PubMed Web of Science ®Google Scholar
• Bell TA, Baker TA, Sauer RT. 2019. Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding. Elife. 8:e46808.
   PubMed Web of Science ®Google Scholar
• Bhandari V, Wong KS, Zhou JL, Mabanglo MF, Batey RA, Houry WA. 2018. The role of ClpP protease in bacterial pathogenesis and human diseases. ACS Chem Biol. 13(6):1413–1425.
   PubMed Web of Science ®Google Scholar
• Bolon DN, Grant RA, Baker TA, Sauer RT. 2004. Nucleotide-dependent substrate handoff from the SspB adaptor to the AAA+ ClpXP protease. Mol Cell. 16(3):343–350.
   PubMed Web of Science ®Google Scholar
• Brötz-Oesterhelt H, Beyer D, Kroll H-P, Endermann R, Ladel C, Schroeder W, Hinzen B, Raddatz S, Paulsen H, Henninger K, et al. 2005. Dysregulation of bacterial proteolytic machinery by a new class of antibiotics. Nat Med. 11(10):1082–1087.
   PubMed Web of Science ®Google Scholar
• Burton BM, Baker TA. 2005. Remodeling protein complexes: insights from the AAA+ unfoldase ClpX and Mu transposase. Protein Sci. 14(8):1945–1954.
   PubMed Web of Science ®Google Scholar
• Burton RE, Siddiqui SM, Kim YI, Baker TA, Sauer RT. 2001. Effects of protein stability and structure on substrate processing by the ClpXP unfolding and degradation machine. Embo J. 20(12):3092–3100.
   PubMed Web of Science ®Google Scholar
• Carney DW, Schmitz KR, Truong JV, Sauer RT, Sello JK. 2014. Restriction of the conformational dynamics of the cyclic acyldepsipeptide antibiotics improves their antibacterial activity. J Am Chem Soc. 136(5):1922–1929.
   PubMed Web of Science ®Google Scholar
• Conlon BP, Nakayasu ES, Fleck LE, LaFleur MD, Isabella VM, Coleman K, Leonard SN, Smith RD, Adkins JN, Lewis K. 2013. Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature. 503(7476):365–370.
   PubMed Web of Science ®Google Scholar
• Cordova JC, Olivares AO, Shin Y, Stinson BM, Calmat S, Schmitz KR, Aubin-Tam ME, Baker TA, Lang MJ, Sauer RT. 2014. Stochastic but highly coordinated protein unfolding and translocation by the ClpXP proteolytic machine. Cell. 158(3):647–658.
   PubMed Web of Science ®Google Scholar
• de la Peña AH, Goodall EA, Gates SN, Lander GC, Martin A. 2018. Substrate-engaged 26S proteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation. Science. 362(6418):eaav0725.
   PubMed Web of Science ®Google Scholar
• Donaldson LW, Wojtyra U, Houry WA. 2003. Solution structure of the dimeric zinc binding domain of the chaperone ClpX. J Biol Chem. 278(49):48991–48996.
   PubMed Web of Science ®Google Scholar
• Dong Y, Zhang S, Wu Z, Li X, Wang WL, Zhu Y, Stoilova-McPhie S, Lu Y, Finley D, Mao Y. 2019. Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome. Nature. 565(7737):49–55.
   PubMed Web of Science ®Google Scholar
• Famulla K, Sass P, Malik I, Akopian T, Kandror O, Alber M, Hinzen B, Ruebsamen-Schaeff H, Kalscheuer R, Goldberg AL, et al. 2016. Acyldepsipeptide antibiotics kill mycobacteria by preventing the physiological functions of the ClpP1P2 protease. Mol Microbiol. 101(2):194–209.
   PubMed Web of Science ®Google Scholar
• Farrell CM, Baker TA, Sauer RT. 2007. Altered specificity of a AAA+ protease. Mol Cell. 25(1):161–166.
   PubMed Web of Science ®Google Scholar
• Fei X, Bell TA, Barkow SR, Baker TA, Sauer RT. 2020. Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates. Elife. 9:e61496.
   PubMed Web of Science ®Google Scholar
• Fei X, Bell TA, Jenni S, Stinson BM, Baker TA, Harrison SC, Sauer RT. 2020. Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate. Elife. 9:e52774.
   PubMed Web of Science ®Google Scholar
• Flynn JM, Levchenko I, Seidel M, Wickner SH, Sauer RT, Baker TA. 2001. Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis. Proc Natl Acad Sci USA. 98(19):10584–10589.
   PubMed Web of Science ®Google Scholar
• Flynn JM, Neher SB, Kim YI, Sauer RT, Baker TA. 2003. Proteomic discovery of cellular substrates of the ClpXP protease reveals five classes of ClpX-recognition signals. Mol Cell. 11(3):671–683.
   PubMed Web of Science ®Google Scholar
• Gatsogiannis C, Balogh D, Merino F, Sieber SA, Raunser S. 2019. Cryo-EM structure of the ClpXP protein degradation machinery. Nat Struct Mol Biol. 26(10):946–954.
   PubMed Web of Science ®Google Scholar
• Gispert S, Parganlija D, Klinkenberg M, Dröse S, Wittig I, Mittelbronn M, Grzmil P, Koob S, Hamann A, Walter M, et al. 2013. Loss of mitochondrial peptidase ClpP leads to infertility, hearing loss plus growth retardation via accumulation of CLPX, mtDNA and inflammatory factors. Hum Mol Genet. 22(24):4871–4887.
   PubMed Web of Science ®Google Scholar
• Glynn SE, Martin A, Nager AR, Baker TA, Sauer RT. 2009. Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine. Cell. 139(4):744–756.
   PubMed Web of Science ®Google Scholar
• Glynn SE, Nager AR, Baker TA, Sauer RT. 2012. Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine. Nat Struct Mol Biol. 19(6):616–622.
   PubMed Web of Science ®Google Scholar
• Gottesman S, Roche E, Zhou Y, Sauer RT. 1998. The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the ssrA-tagging system. Genes Dev. 12(9):1338–1347.
   PubMed Web of Science ®Google Scholar
• Hanson PI, Whiteheart SW. 2005. AAA+ proteins: have engine, will work. Nat Rev Mol Cell Biol. 6(7):519–529.
   PubMed Web of Science ®Google Scholar
• Hersch GL, Burton RE, Bolon DN, Baker TA, Sauer RT. 2005. Asymmetric interactions of ATP with the AAA+ ClpX6 unfoldase: allosteric control of a protein machine. Cell. 121(7):1017–1027.
   PubMed Web of Science ®Google Scholar
• Iosefson O, Nager AR, Baker TA, Sauer RT. 2015. Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine. Nat Chem Biol. 11(3):201–206.
   PubMed Web of Science ®Google Scholar
• Iosefson O, Olivares AO, Baker TA, Sauer RT. 2015. Dissection of axial-pore loop function during unfolding and translocation by a AAA+ proteolytic machine. Cell Rep. 12(6):1032–1041.
   PubMed Web of Science ®Google Scholar
• Jenal U, Fuchs T. 1998. An essential protease involved in bacterial cell-cycle control. Embo J. 17(19):5658–5669.
   PubMed Web of Science ®Google Scholar
• Joshi SA, Hersch GL, Baker TA, Sauer RT. 2004. Communication between ClpX and ClpP during substrate processing and degradation. Nat Struct Mol Biol. 11(5):404–411.
   PubMed Web of Science ®Google Scholar
• Kahne SC, Darwin KH. 2021. Structural determinants of regulated proteolysis in pathogenic bacteria by ClpP and the proteasome. Curr Opin Struct Biol. 67:120–126.
   PubMed Web of Science ®Google Scholar
• Kang SG, Dimitrova MN, Ortega J, Ginsburg A, Maurizi MR. 2005. Human mitochondrial ClpP is a stable heptamer that assembles into a tetradecamer in the presence of ClpX. J Biol Chem. 280(42):35424–35432.
   PubMed Web of Science ®Google Scholar
• Kardon JR, Yien YY, Huston NC, Branco DS, Hildick-Smith GJ, Rhee KY, Paw BH, Baker TA. 2015. Mitochondrial ClpX activates a key enzyme for heme biosynthesis and erythropoiesis. Cell. 161(4):858–867.
   PubMed Web of Science ®Google Scholar
• Keiler KC, Waller PR, Sauer RT. 1996. Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA. Science. 271(5251):990–993.
   PubMed Web of Science ®Google Scholar
• Keiler KC. 2015. Mechanisms of ribosome rescue in bacteria. Nat Rev Microbiol. 13(5):285–297.
   PubMed Web of Science ®Google Scholar
• Kenniston JA, Baker TA, Fernandez JM, Sauer RT. 2003. Linkage between ATP consumption and mechanical unfolding during the protein processing reactions of an AAA+ degradation machine. Cell. 114(4):511–520.
   PubMed Web of Science ®Google Scholar
• Kenniston JA, Baker TA, Sauer RT. 2005. Partitioning between unfolding and release of native domains during ClpXP degradation determines substrate selectivity and partial processing. Proc Natl Acad Sci USA. 102(5):1390–1395.
   PubMed Web of Science ®Google Scholar
• Kenniston JA, Burton RE, Siddiqui SM, Baker TA, Sauer RT. 2004. Effects of local protein stability and the geometric position of the substrate degradation tag on the efficiency of ClpXP denaturation and degradation. J Struct Biol. 146(1-2):130–140.
   PubMed Web of Science ®Google Scholar
• Kessel M, Maurizi MR, Kim B, Kocsis E, Trus BL, Singh SK, Steven AC. 1995. Homology in structural organization between E. coli ClpAP protease and the eukaryotic 26 S proteasome. J Mol Biol. 250(5):587–594.
   PubMed Web of Science ®Google Scholar
• Kim DY, Kim KK. 2003. Crystal structure of ClpX molecular chaperone from Helicobacter pylori. J Biol Chem. 278(50):50664–50670.
   PubMed Web of Science ®Google Scholar
• Kim S, Zuromski KL, Bell TA, Sauer RT, Baker TA. 2020. ClpAP proteolysis does not require rotation of the ClpA unfoldase relative to ClpP. Elife. 9:e61451.
   PubMed Web of Science ®Google Scholar
• Kim YI, Burton RE, Burton BM, Sauer RT, Baker TA. 2000. Dynamics of substrate denaturation and translocation by the ClpXP degradation machine. Mol Cell. 5(4):639–648.
   PubMed Web of Science ®Google Scholar
• Kim YI, Levchenko I, Fraczkowska K, Woodruff RV, Sauer RT, Baker TA. 2001. Molecular determinants of complex formation between Clp/Hsp100 ATPases and the ClpP peptidase. Nat Struct Biol. 8(3):230–233.
   PubMedGoogle Scholar
• Kimber MS, Yu AY, Borg M, Leung E, Chan HS, Houry WA. 2010. Structural and theoretical studies indicate that the cylindrical protease ClpP samples extended and compact conformations. Structure. 18(7):798–808.
   PubMed Web of Science ®Google Scholar
• Kirstein J, Hoffmann A, Lilie H, Schmidt R, Rübsamen-Waigmann H, Brötz-Oesterhelt H, Mogk A, Turgay K. 2009. The antibiotic ADEP reprogrammes ClpP, switching it from a regulated to an uncontrolled protease. EMBO Mol Med. 1(1):37–49.
   PubMed Web of Science ®Google Scholar
• Konovalova A, Søgaard-Anderse L, Kroos L. 2014. Regulated proteolysis in bacterial development. FEMS Microbiol Rev. 38(3):493–522.
   PubMed Web of Science ®Google Scholar
• Kraut DA. 2013. Slippery substrates impair ATP-dependent protease function by slowing unfolding. J Biol Chem. 288(48):34729–34735.
   PubMed Web of Science ®Google Scholar
• Lee BG, Park EY, Lee KE, Jeon H, Sung KH, Paulsen H, Rübsamen-Schaeff H, Brötz-Oesterhelt H, Song HK. 2010. Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism. Nat Struct Mol Biol. 17(4):471–478.
   PubMed Web of Science ®Google Scholar
• Lee C, Schwartz MP, Prakash S, Iwakura M, Matouschek A. 2001. ATP-dependent proteases degrade their substrates by processively unraveling them from the degradation signal. Mol Cell. 7(3):627–637.
   PubMed Web of Science ®Google Scholar
• Lee ME, Baker TA, Sauer RT. 2010. Control of substrate gating and translocation into ClpP by channel residues and ClpX binding. J Mol Biol. 399(5):707–718.
   PubMed Web of Science ®Google Scholar
• Levchenko I, Seidel M, Sauer RT, Baker TA. 2000. A specificity-enhancing factor for the ClpXP degradation machine. Science. 289(5488):2354–2356.
   PubMed Web of Science ®Google Scholar
• Li DH, Chung YS, Gloyd M, Joseph E, Ghirlando R, Wright GD, Cheng YQ, Maurizi MR, Guarné A, Ortega J. 2010. Acyldepsipeptide antibiotics induce the formation of a structured axial channel in ClpP: a model for the ClpX/ClpA-bound state of ClpP. Chem Biol. 17(9):959–969.
   PubMedGoogle Scholar
• Li M, Kandror O, Akopian T, Dharkar P, Wlodawer A, Maurizi MR, Goldberg AL. 2016. Structure and functional properties of the active form of the proteolytic complex, ClpP1P2, from Mycobacterium tuberculosis. J Biol Chem. 291(14):7465–7476.
   PubMed Web of Science ®Google Scholar
• Liu K, Ologbenla A, Houry WA. 2014. Dynamics of the ClpP serine protease: a model for self-compartmentalized proteases. Crit Rev Biochem Mol Biol. 49(5):400–412.
   PubMed Web of Science ®Google Scholar
• Lopez KE, Rizo AN, Tse E, Lin J, Scull NW, Thwin AC, Lucius AL, Shorter J, Southworth DR. 2020. Conformational plasticity of the ClpAP AAA+ protease couples protein unfolding and proteolysis. Nat Struct Mol Biol. 27(5):406–416.
   PubMed Web of Science ®Google Scholar
• Luo B, Ma Y, Zhou Y, Zhang N, Luo Y. 2021. Human ClpP protease, a promising therapy target for diseases of mitochondrial dysfunction. Drug Discov Today. 26(4):968–981.
   PubMed Web of Science ®Google Scholar
• Mahmoud SA, Chien P. 2018. Regulated proteolysis in bacteria. Annu Rev Biochem. 87:677–696.
   PubMed Web of Science ®Google Scholar
• Maillard RA, Chistol G, Sen M, Righini M, Tan J, Kaiser CM, Hodges C, Martin A, Bustamante C. 2011. ClpX(P) generates mechanical force to unfold and translocate its protein substrates. Cell. 145(3):459–469.
   PubMed Web of Science ®Google Scholar
• Martin A, Baker TA, Sauer RT. 2007. Distinct static and dynamic interactions control ATPase-peptidase communication in a AAA+ protease. Mol Cell. 27(1):41–52.
   PubMed Web of Science ®Google Scholar
• Martin A, Baker TA, Sauer RT. 2008a. Diverse pore loops of the AAA+ ClpX machine mediate unassisted and adaptor-dependent recognition of ssrA-tagged substrates. Mol Cell. 29(4):441–450.
   PubMed Web of Science ®Google Scholar
• Martin A, Baker TA, Sauer RT. 2008b. Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding. Nat Struct Mol Biol. 15(11):1147–1151.
   PubMed Web of Science ®Google Scholar
• Maurizi MR, Clark WP, Katayama Y, Rudikoff S, Pumphrey J, Bowers B, Gottesman S. 1990. Sequence and structure of Clp P, the proteolytic component of the ATP-dependent Clp protease of Escherichia coli. J Biol Chem. 265(21):12536–12545.
   PubMed Web of Science ®Google Scholar
• Maurizi MR, Clark WP, Kim SH, Gottesman S. 1990. Clp P represents a unique family of serine proteases. J Biol Chem. 265(21):12546–12552.
   PubMed Web of Science ®Google Scholar
• Mawla GD, Hall BM, Cárcamo-Oyarce G, Grant RA, Zhang JJ, Kardon JR, Ribbeck K, Sauer RT, Baker TA. 2021. ClpP1P2 peptidase activity promotes biofilm formation in Pseudomonas aeruginosa. Mol Microbiol. 115(6):1094–1109.
   PubMed Web of Science ®Google Scholar
• McGinness KE, Bolon DN, Kaganovich M, Baker TA, Sauer RT. 2007. Altered tethering of the SspB adaptor to the ClpXP protease causes changes in substrate delivery. J Biol Chem. 282(15):11465–11473.
   PubMed Web of Science ®Google Scholar
• Moore SD, Sauer RT. 2007. The tmRNA system for translational surveillance and ribosome rescue. Annu Rev Biochem. 76:101–124.
   PubMed Web of Science ®Google Scholar
• Moreno-Cinos C, Goossens K, SaladoI G, Van Der Veken PD, Winter H, Augustyns K. 2019. ClpP protease, a promising antimicrobial target. Int J Mol Sci. 20(9):2232.
   Web of Science ®Google Scholar
• Neher SB, Sauer RT, Baker TA. 2003. Distinct peptide signals in the UmuD and UmuD' subunits of UmuD/D' mediate tethering and substrate processing by the ClpXP protease. Proc Natl Acad Sci USA. 100(23):13219–13224.
   PubMed Web of Science ®Google Scholar
• Neuwald A, Aravind L, Spouge JL, Koonin EV. 1999. AAA+: a class of chaperone-like ATPases associated with assembly, operation, and disassembly of protein complexes. Genome Res. 9(1):27–43.
   PubMed Web of Science ®Google Scholar
• Ogura T, Wilkinson AJ. 2001. AAA+ superfamily ATPases: common structure-diverse function. Genes Cells. 6(7):575–597.
   PubMed Web of Science ®Google Scholar
• Olivares AO, Baker TA, Sauer RT. 2018. Mechanical protein unfolding and degradation. Annu Rev Physiol. 80:413–429.
   PubMed Web of Science ®Google Scholar
• Olivares AO, Kotamarthi HC, Stein BJ, Sauer RT, Baker TA. 2017. Effect of directional pulling on mechanical protein degradation by ATP-dependent proteolytic machines. Proc Natl Acad Sci USA. 114(31):E6306–E6313.
   PubMed Web of Science ®Google Scholar
• Ortega J, Lee HS, Maurizi MR, Steven AC. 2002. Alternating translocation of protein substrates from both ends of ClpXP protease. Embo J. 21(18):4938–4949.
   PubMed Web of Science ®Google Scholar
• Park EY, Lee BG, Hong SB, Kim HW, Jeon H, Song HK. 2007. Structural basis of SspB-tail recognition by the zinc binding domain of ClpX. J Mol Biol. 367(2):514–526.
   PubMed Web of Science ®Google Scholar
• Pavelka A, Sebestova E, Kozlikova B, Brezovsky J, Sochor J, Damborsky J. 2016. CAVER: algorithms for analyzing dynamics of tunnels in macromolecules. IEEE/ACM Trans Comput Biol Bioinform. 13(3):505–517.
   PubMed Web of Science ®Google Scholar
• Puchades C, Rampello AJ, Shin M, Giuliano CJ, Wiseman RL, Glynn SE, Lander GC. 2017. Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing. Science. 358(6363):eaao0464.
   PubMed Web of Science ®Google Scholar
• Puchades C, Sandate CR, Lander GC. 2020. The molecular principles governing the activity and functional diversity of AAA+ proteins. Nat Rev Mol Cell Biol. 21(1):43–58.
   PubMed Web of Science ®Google Scholar
• Ripstein ZA, Vahidi S, Houry WA, Rubinstein JL, Kay LE. 2020. A processive rotary mechanism couples substrate unfolding and proteolysis in the ClpXP degradation machinery. Elife. 9:e52158.
   PubMed Web of Science ®Google Scholar
• Ripstein ZA, Vahidi S, Rubinstein JL, Kay LE. 2020. A pH-dependent conformational switch controls N. meningitidis ClpP protease function. J Am Chem Soc. 142(49):20519–20523.
   PubMed Web of Science ®Google Scholar
• Roche ED, Sauer RT. 1999. SsrA-mediated peptide tagging caused by rare codons and tRNA scarcity. Embo J. 18(16):4579–4589.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Aliaga P, Ramirez L, Kim F, Bustamante C, Martin A. 2016. Substrate-translocating loops regulate mechanochemical coupling and power production in AAA+ protease ClpXP. Nat Struct Mol Biol. 23(11):974–981.
   PubMed Web of Science ®Google Scholar
• San Martín Á, Rodriguez-Aliaga P, Molina JA, Martin A, Bustamante C, Baez M. 2017. Knots can impair protein degradation by ATP-dependent proteases. Proc Natl Acad Sci USA. 114(37):9864–9869.
   PubMed Web of Science ®Google Scholar
• Sauer RT, Baker TA. 2011. AAA+ proteases: ATP-fueled machines of protein destruction. Annu Rev Biochem. 80:587–612.
   PubMed Web of Science ®Google Scholar
• Saunders RA, Stinson BM, Baker TA, Sauer RT. 2020. Multistep substrate binding and engagement by the AAA+ ClpXP protease. Proc Natl Acad Sci USA. 117(45):28005–28013.
   PubMed Web of Science ®Google Scholar
• Schmitz KR, Carney DW, Sello JK, Sauer RT. 2014. Crystal structure of Mycobacterium tuberculosis ClpP1P2 suggests a model for peptidase activation by AAA+ partner binding and substrate delivery. Proc Natl Acad Sci USA. 111(43):E4587–4595.
   PubMed Web of Science ®Google Scholar
• Sen M, Maillard RA, Nyquist K, Rodriguez-Aliaga P, Pressé S, Martin A, Bustamante C. 2013. The ClpXP protease unfolds substrates using a constant rate of pulling but different gears. Cell. 155(3):636–646.
   PubMed Web of Science ®Google Scholar
• Siddiqui SM, Sauer RT, Baker TA. 2004. Role of the processing pore of the ClpX AAA+ ATPase in the recognition and engagement of specific protein substrates. Genes Dev. 18(4):369–374.
   PubMed Web of Science ®Google Scholar
• Singh SK, Grimaud R, Hoskins JR, Wickner S, Maurizi MR. 2000. Unfolding and internalization of proteins by the ATP-dependent proteases ClpXP and ClpAP. Proc Natl Acad Sci USA. 97(16):8898–8903.
   PubMed Web of Science ®Google Scholar
• Singh SK, Rozycki J, Ortega J, Ishikawa T, Lo J, Steven AC, Maurizi MR. 2001. Functional domains of the ClpA and ClpX molecular chaperones identified by limited proteolysis and deletion analysis. J Biol Chem. 276(31):29420–29429.
   PubMed Web of Science ®Google Scholar
• Sivertsson EM, Jackson SE, Itzhaki LS. 2019. The AAA+ protease ClpXP can easily degrade a 31 and a 52-knotted protein. Sci Rep. 9(1):2421.
   PubMedGoogle Scholar
• Sprangers R, Gribun A, Hwang PM, Houry WA, Kay LE. 2005. Quantitative NMR spectroscopy of supramolecular complexes: dynamic side pores in ClpP are important for product release. Proc Natl Acad Sci USA. 102(46):16678–16683.
   PubMed Web of Science ®Google Scholar
• Sriramoju MK, Chen Y, Hsu SD. 2020. Protein knots provide mechano-resilience to an AAA+ protease-mediated proteolysis with profound ATP energy expenses. Biochim Biophys Acta Proteins Proteom. 1868(2):140330.
   PubMed Web of Science ®Google Scholar
• Stinson BM, Nager AR, Glynn SE, Schmitz KR, Baker TA, Sauer RT. 2013. Nucleotide binding and conformational switching in the hexameric ring of a AAA+ machine. Cell. 153(3):628–639.
   PubMed Web of Science ®Google Scholar
• Striebel F, Kress W, Weber-Ban E. 2009. Controlled destruction: AAA+ ATPases in protein degradation from bacteria to eukaryotes. Curr Opin Struct Biol. 19(2):209–217.
   PubMed Web of Science ®Google Scholar
• Thompson MW, Maurizi MR. 1994. Activity and specificity of Escherichia coli ClpAP protease in cleaving model peptide substrates. J Biol Chem. 269(27):18201–18208.
   PubMed Web of Science ®Google Scholar
• Too PH, Erales J, Simen JD, Marjanovic A, Coffino P. 2013. Slippery substrates impair function of a bacterial protease ATPase by unbalancing translocation versus exit. J Biol Chem. 288(19):13243–13257.
   PubMed Web of Science ®Google Scholar
• Tremblay CY, Vass RH, Vachet RW, Chien P. 2020. The cleavage profile of protein substrates by ClpXP reveals deliberate starts and pauses. Biochemistry. 59(44):4294–4301.
   PubMed Web of Science ®Google Scholar
• Vass RH, Chien P. 2013. Critical clamp loader processing by an essential AAA+ protease in Caulobacter crescentus. Proc Natl Acad Sci USA. 110(45):18138–18143.
   PubMed Web of Science ®Google Scholar
• Wang J, Hartling JA, Flanagan JM. 1997. The structure of ClpP at 2.3 Å resolution suggests a model for ATP-dependent proteolysis. Cell. 91(4):447–456.
   PubMed Web of Science ®Google Scholar
• Wojtyra UA, Thibault G, Tuite A, Houry WA. 2003. The N-terminal zinc binding domain of ClpX is a dimerization domain that modulates the chaperone function. J Biol Chem. 278(49):48981–48990.
   PubMed Web of Science ®Google Scholar
• Yien YY, Ducamp S, van der Vorm LN, Kardon JR, Manceau H, Kannengiesser C, Bergonia HA, Kafina MD, Karim Z, Gouya L, et al. 2017. Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria. Proc Natl Acad Sci USA. 114(38):E8045–E8052.
   PubMed Web of Science ®Google Scholar
• Zeiler E, Korotkov VS, Lorenz-Baath K, Böttcher T, Sieber SA. 2012. Development and characterization of improved β-lactone-based anti-virulence drugs targeting ClpP. Bioorg Med Chem. 20(2):583–591.
   PubMed Web of Science ®Google Scholar
• Zhang J, Ye F, Lan L, Jiang H, Luo C, Yang CG. 2011. Structural switching of Staphylococcus aureus Clp protease: a key to understanding protease dynamics. J Biol Chem. 286(43):37590–37601.
   PubMed Web of Science ®Google Scholar
• Zhang S, Mao Y. 2020. AAA+ ATPases in protein degradation: structures, functions and mechanisms. Biomolecules. 10(4):629.
   Web of Science ®Google Scholar