Abstract
Inclusion body–associated proteins IbpA and IbpB of MW 16 KDa are the two small heat-shock proteins (sHSPs) of Escherichia coli, and they have only holding, but not folding, chaperone activity. In vitro holdase activity of IbpB is more than that of IbpA, and in combination, they synergise. Both IbpA and IbpB monomers first form homodimers, which as building blocks subsequently oligomerize to make heavy oligomers with MW of MDa range; for IbpB, the MW range of heavy oligomers is 2.0–3.0 MDa, whereas for IbpA oligomers, the values in MDa are not so specified/reported. By temperature upshift, such large oligomers of IbpB, but not of IbpA, dissociate to make relatively small oligomeric assemblies of MW around 600–700KDa. The larger oligomers of IbpB are assumed to be inactive storage form, which on facing heat or oxidative stress dissociate into smaller oligomers of ATP-independent holding chaperone activity. These smaller oligomers bind with stress-induced partially denatured/unfolded and thereby going to be aggregated proteins, to give them protection against permanent damage and aggregation. On withdrawal of stress, IbpB transfers the bound substrate protein to the ATP-dependent bi-chaperone system DnaKJE-ClpB, having both holdase and foldase properties, to finally refold the protein. Of the two sHSPs IbpA and IbpB of E. coli, this review covers the recent advances in research on IbpB only.
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References
Akerfelt M, Morimoto RI, Sistonen L (2010) Heat shock factors: integrators of cell stress, development and lifespan. Nat Rev Mol Cell Biol 11(8):545–555. https://doi.org/10.1038/nrm2938
Alagar Boopathy LR, Jacob-Tomas S, Alecki C, Vera M (2022) Mechanisms tailoring the expression of heat shock proteins to proteostasis challenges. J Biol Chem 298(5):101796. https://doi.org/10.1016/j.jbc.2022.101796
Anckar J, Sistonen L (2011) Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annu Rev Biochem 80:1089–1115. https://doi.org/10.1146/annurev-biochem-060809-095203
Aolymat I, Hatmal MM, Olaimat AN (2023) The emerging role of heat shock factor 1 (HSF1) and heat shock proteins (HSPs) in Ferroptosis. Pathophysiol: Pathophysiol 30(1):63–82. https://doi.org/10.3390/pathophysiology30010007
Aquilina JA, Shrestha S, Morris AM, Ecroyd H (2013) Structural and functional aspects of hetero-oligomers formed by the small heat shock proteins αB-crystallin and HSP27. J Biol Chem 288(19):13602–13609. https://doi.org/10.1074/jbc.M112.443812
Asthana A, Bollapalli M, Tangirala R, Bakthisaran R, Mohan Rao CH (2014) Hsp27 suppresses the Cu(2+)-induced amyloidogenicity, redox activity, and cytotoxicity of α-synuclein by metal ion strip**. Free Radic Biol Med 72:176–190. https://doi.org/10.1016/j.freeradbiomed.2014.04.012
Augusteyn RC (2004) α-crystallin: a review of its structure and function. Clin Exp Optom 87(6):356–366. https://doi.org/10.1111/j.1444-0938.2004.tb03095.x
Bakthisaran R, Tangirala R, Rao CM (2015) Small heat shock proteins: role in cellular functions and pathology. Biochim Biophys Acta 1854(4):291–319. https://doi.org/10.1016/j.bbapap.2014.12.019
Basha E, O’Neill H, Vierling E (2012) Small heat shock proteins and α-crystallins: dynamic proteins with flexible functions. Trends Biochem Sci 37(3):106–117. https://doi.org/10.1016/j.tibs.2011.11.005
Bellanger T, Weidmann S (2023) Is the lipochaperone activity of sHSP a key to the stress response encoded in its primary sequence? Cell Stress Chaperones 28:21–33. https://doi.org/10.1007/s12192-022-01308-7
Bepperling A, Alte F, Kriehuber T, Braun N, Weinkauf S, Groll M, Haslbeck M, Buchner J (2012) Alternative bacterial two-component small heat shock protein systems. Proc Natl Acad Sci USA 109(50):20407–20412. https://doi.org/10.1073/pnas.1209565109
Bhattacharjee S, Dasgupta R, Bagchi A (2015) The small heat-shock proteins IbpA and IbpB in E. coli: the small ones with a big role. Curr Chem Biol 9(2):84–96
Bissonnette SA, Rivera-Rivera I, Sauer RT, Baker TA (2010) The IbpA and IbpB small heat-shock proteins are substrates of the AAA+ Lon protease. Mol Microbiol 75(6):1539–1549. https://doi.org/10.1111/j.1365-2958.2010.07070.x
Cheng G, Basha E, Wysocki VH, Vierling E (2008) Insights into small heat shock protein and substrate structure during chaperone action derived from hydrogen/deuterium exchange and mass spectrometry. J Biol Chem 283(39):26634–26642. https://doi.org/10.1074/jbc.M802946200
Cheng Y, Miwa T, Taguchi H (2023) Self-regulatory function of bacterial small heat shock protein IbpA through mRNA binding is conferred by a conserved arginine. CSH-bioRxiv:538363. https://doi.org/10.1101/2023.04.26.538363
Chernova LS, Bogachev MI, Chasov VV, Vishnyakov IE, Kayumov AR (2020) N- and C-terminal regions of the small heat shock protein IbpA from Acholeplasma laidlawii competitively govern its oligomerization pattern and chaperone-like activity. RSC Adv 10(14):8364–8376. https://doi.org/10.1039/c9ra10172a
Chhabra SR, He Q, Huang KH, Gaucher SP, Alm EJ, He Z, Hadi MZ, Hazen TC, Wall JD, Zhou J, Arkin AP, Singh AK (2006) Global analysis of heat shock response in Desulfovibrio vulgaris Hildenborough. J Bacteriol 188(5):1817–1828. https://doi.org/10.1128/JB.188.5.1817-1828.2006
Faust O, Abayev-Avraham M, Wentink AS, Maurer M, Nillegoda NB, London N, Bukau B, Rosenzweig R (2020) HSP40 proteins use class-specific regulation to drive HSP70 functional diversity. Nature 587(7834):489–494. https://doi.org/10.1038/s41586-020-2906-4
Feng XH, Zhang HX, Ali M, Gai WX, Cheng GX, Yu QH, Yang SB, Li XX, Gong ZH (2019) A small heat shock protein CaHsp25.9 positively regulates heat, salt, and drought stress tolerance in pepper (Capsicum annuum L.). Plant Physiol Biochem 142:151–162. https://doi.org/10.1016/j.plaphy.2019.07.001
Franzmann TM, Menhom P, Walter S, Buchner J (2008) Activation of the chaperone Hsp26 is controlled by the rearrangement of its thermosensor domain. Mol Cell 29:207–216. https://doi.org/10.1016/j.molcel.2007.11.025
Gaestel M (2002) sHsp-phosphorylation: enzymes, signaling pathways and functional implications. Prog Mol Subcell Biol 28:151–169. https://doi.org/10.1007/978-3-642-56348-5_8
Gaubig LC, Waldminghaus T, Narberhaus F (2011) Multiple layers of control govern expression of the Escherichia coli ibpAB heat-shock operon. Microbiology 157(1):66–76. https://doi.org/10.1099/mic.0.043802-0
Guzzo J (2012) Biotechnical applications of small heat shock proteins from bacteria. Int J Biochem Cell Biol 44(10):1698–1705. https://doi.org/10.1016/j.biocel.2012.06.007
Haley DA, Bova MP, Huang QL, Mchaourab HS, Stewart PL (2000) Small heat-shock protein structures reveal a continuum from symmetric to variable assemblies. J Mol Biol 298(2):261–272. https://doi.org/10.1006/jmbi.2000.3657
Haslbeck M, Vierling E (2015) A first line of stress defense: small heat shock proteins and their function in protein homeostasis. J Mol Biol 427(7):1537–1548. https://doi.org/10.1016/j.jmb.2015.02.002
Haslbeck M, Miess A, Stromer T, Walter S, Buchner J (2005) Disassembling protein aggregates in the yeast cytosol. J Biol Chem 280(25):23861–23868. https://doi.org/10.1074/jbc.m502697200
Haslbeck M, Weinkauf S, Buchner J (2019) Small heat shock proteins: simplicity meets complexity. J Biol Chem 294(6):2121–2132. https://doi.org/10.1074/jbc.REV118.002809
Hibshman JD, Carra S, Goldstein B (2023) Tardigrade small heat shock proteins can limit desiccation-induced protein aggregation. Commun Biol 6(1):121. https://doi.org/10.1038/s42003-023-04512-y
Hilton GR, Lioe H, Stengel F, Baldwin AJ, Benesch JLP (2013) Small heat-shock proteins: paramedics of the cell. Top Curr Chem 328:69–98. https://doi.org/10.1007/128_2012_324
Hu C, Yang J, Qi Z, Wu H, Wang B, Zou F, Mei H, Liu J, Wang W, Liu Q (2022) Heat shock proteins: biological functions, pathological roles, and therapeutic opportunities. MedComm 3(3):161. https://doi.org/10.1002/mco2.161
Janowska MK, Baughman HER, Woods CN, Klevit RE (2019) Mechanisms of small heat shock proteins. Cold Spring Harb Perspect Biol 11(10):34025. https://doi.org/10.1101/cshperspect.a034025
Kędzierska-Mieszkowska S, Zolkiewski M (2021) Hsp100 molecular chaperone ClpB and its role in virulence of bacterial pathogens. Int J Mol Sci 22(10):5319. https://doi.org/10.3390/ijms22105319
Kirstein J, Molière N, Dougan DA, Turgay K (2009) Adapting the machine: adaptor proteins for Hsp100/Clp and AAA+ proteases. Nat Rev Microbiol 7(8):589–599. https://doi.org/10.1038/nrmicro2185
Kitagawa M, Matsumura Y, Tsuchido T (2000) Small heat shock proteins, IbpA and IbpB, are involved in resistances to heat and superoxide stresses in Escherichia coli. FEMS Microbiol Lett 184(2):165–171. https://doi.org/10.1111/j.1574-6968.2000.tb09009.x
Kitagawa M, Miyakawa M, Matsumura Y, Tsuchido T (2002) Escherichia coli small heat shock proteins, IbpA and IbpB, protect enzymes from inactivation by heat and oxidants. Eur J Biochem 269(12):2907–2917. https://doi.org/10.1046/j.1432-1033.2002.02958.x
Klevit RE (2020) Peeking from behind the veil of enigma: emerging insights on small heat shock protein structure and function. Cell Stress Chaperones 25(4):573–580. https://doi.org/10.1007/s12192-020-01092-2
Kriehuber T, Rattei T, Weinmaier T, Bepperling A, Haslbeck M, Buchner J (2010) Independent evolution of the core domain and its flanking sequences in small heat shock proteins. FASEB J 24(10):3633–3642. https://doi.org/10.1096/fj.10-156992
Kuczynska-Wisnik D, Kçdzierska S, Matuszewska E, Lund P, Taylor A, Lipinska B, Laskowska E (2002) The Escherichia coli small heat-shock proteins IbpA and IbpB prevent the aggregation of endogenous proteins denatured in vivo during extreme heat shock. Microbiology 148(6):1757–1765. https://doi.org/10.1099/00221287-148-6-1757
Lelj-Garolla B, Mauk AG (2005) Self-association of a small heat shock protein. J Mol Biol 345(3):631–642. https://doi.org/10.1016/j.jmb.2004.10.056
Lethanh H, Neubauer P, Hoffmann F (2005) The small heat-shock proteins IbpA and IbpB reduce the stress load of recombinant Escherichia coli and delay degradation of inclusion bodies. Microb Cell Fact 4(1):6. https://doi.org/10.1186/1475-2859-4-6
Matuszewska M, Kuczyńska-Wiśnik D, Laskowska E, Liberek K (2005) The small heat shock protein IbpA of Escherichia coli cooperates with IbpB in stabilization of thermally aggregated proteins in a disaggregation competent state. J Biol Chem 280(13):12292–12298. https://doi.org/10.1074/jbc.M412706200
Miwa T, Taguchi H (2023) The Escherichia coli small heat shock protein IbpA plays a role in regulating the heat shock response by controlling the translation of σ32, CSH-bioRxiv:534623 https://doi.org/10.1101/2023.03.28.534623
Miwa T, Chadani Y, Taguchi H (2021) Escherichia coli small heat shock protein IbpA is an aggregation-sensor that self-regulates its own expression at posttranscriptional levels. Mol Microbiol 115(1):142–156. https://doi.org/10.1111/mmi.14606
Mogk A, Deuerling E, Vorderwülbecke S, Vierling E, Bukau B (2003) Small heat shock proteins, ClpB and the DnaK system form a functional triade in reversing protein aggregation. Mol Microbiol 50(2):585–595. https://doi.org/10.1046/j.1365-2958.2003.03710.x
Mogk A, Schlieker C, Friedrich KL, Schönfeld HJ, Vierling E, Bukau B (2003) Refolding of substrates bound to small Hsps relies on a disaggregation reaction mediated most efficiently by ClpB/DnaK. J Biol Chem 278(33):31033–31042. https://doi.org/10.1074/jbc.M303587200
Mogk A, Ruger-Herreros C, Bukau B (2019) Cellular functions and mechanisms of action of small heat shock proteins. Annu Rev Microbiol 73:89–110. https://doi.org/10.1146/annurev-micro-020518-115515
Molière N, Turgay K (2009) Chaperone-protease systems in regulation and protein quality control in Bacillus subtilis. Res Microbiol 160(9):637–644. https://doi.org/10.1016/j.resmic.2009.08.020
Mymrikov EV, Seit-Nebi AS, Gusev NB (2011) Large potentials of small heat shock proteins. Physiol Rev 91(4):1123–1159. https://doi.org/10.1152/physrev.00023.2010
Mymrikov EV, Riedl M, Peters C, Weinkauf S, Haslbeck M, Buchner J (2020) Regulation of small heat-shock proteins by hetero-oligomer formation. J Biol Chem 295(1):158–169. https://doi.org/10.1074/jbc.RA119.011143
Nunes JM, Mayer-Hartl M, Hartl FU, Müller DJ (2015) Action of the Hsp70 chaperone system observed with single proteins. Nat Commun 6:6307. https://doi.org/10.1038/ncomms7307
Obuchowski I, Liberek K (2020) Small but mighty: a functional look at bacterial sHSPs. Cell Stress Chaperones 25:593–600. https://doi.org/10.1007/s12192-020-01094-0
Obuchowski I, Piróg A, Stolarska M, Tomiczek B, Liberek K (2019) Duplicate divergence of two bacterial small heat shock proteins reduces the demand for Hsp70 in refolding of substrates. PLoS Genet 15(10):e1008479. https://doi.org/10.1371/journal.pgen.1008479
Obuchowski I, Karaś P, Liberek K (2021) The small ones matter-shsps in the bacterial chaperone network. Front Mol Biosci 8:666893. https://doi.org/10.3389/fmolb.2021.666893
Patra M, Roy SS, Dasgupta R, Basu T (2015) GroEL to DnaK chaperone network behind the stability modulation of σ(32) at physiological temperature in Escherichia coli. FEBS Lett 589(24):4047–4052. https://doi.org/10.1016/j.febslet.2015.10.034
Piróg A, Cantini F, Nierzwicki Ł, Obuchowski I, Tomiczek B, Czub J, Liberek K (2021) Two bacterial small heat shock proteins, IbpA and IbpB, form a functional heterodimer. J Mol Biol 433(15):167054. https://doi.org/10.1016/j.jmb.2021.167054
Pulido P, Llamas E, Llorente B, Ventura S, Wright LP, Rodríguez-Concepción M (2016) Specific Hsp100 chaperones determine the fate of the first enzyme of the plastidial isoprenoid pathway for either refolding or degradation by the stromal Clp protease in Arabidopsis. PLoS Genet 12(1):1005824. https://doi.org/10.1371/journal.pgen.1005824
Queraltó C, Álvarez R Ortega C, Díaz-Yáñez F, Paredes-Sabja D, Gil F (2023) Role and regulation of Clp proteases: a target against gram-positive bacteria. Bacteria 2(1):1. https://doi.org/10.3390/bacteria2010002
Ratajczak E, Zietkiewicz S, Liberek K (2009) Distinct activities of Escherichia coli small heat shock proteins IbpA and IbpB promote efficient protein disaggregation. J Mol Biol 386(1):178–189. https://doi.org/10.1016/j.jmb.2008.12.009
Ritossa F (1962) A new puffing pattern induced by temperature shock and DNP in drosophila. Experientia 18(12):571–573. https://doi.org/10.1007/BF02172188
Roncarati D, Scarlato V (2017) Regulation of heat-shock genes in bacteria: from signal sensing to gene expression output. FEMS Microbiol Rev 41(4):549–574. https://doi.org/10.1093/femsre/fux015
Rosenzweig R, Nillegoda NB, Mayer MP, Bukau B (2019) The Hsp70 chaperone network. Nat Rev Mol Cell Biol 20(11):665–680. https://doi.org/10.1038/s41580-019-0133-3
Sachdeva P, Misra R, Tyagi AK, Singh Y (2010) The sigma factors of Mycobacterium tuberculosis: regulation of the regulators. FEBS J 277(3):605–626. https://doi.org/10.1111/j.1742-4658.2009.07479.x
Scharf KD, Berberich T, Ebersberger I, Nover L (2012) The plant heat stress transcription factor (Hsf) family: structure, function and evolution. Biochim Biophys Acta 1819(2):104–119. https://doi.org/10.1016/j.bbagrm.2011.10.002
Schumann W (2016) Regulation of bacterial heat shock stimulons. Cell Stress Chaperones 21(6):959–968. https://doi.org/10.1007/s12192-016-0727-z
Shan Q, Ma F, Wei J, Li H, Ma H, Sun P (2020) Physiological functions of heat shock proteins. Curr Protein Pept Sci 21(8):751–760. https://doi.org/10.2174/1389203720666191111113726
Shearstone JR, Baneyx F (1999) Biochemical characterization of the small heat shock protein IbpB from Escherichia coli. J Biol Chem 274(15):9937–9945. https://doi.org/10.1074/jbc.274.15.9937
Singha Roy S, Patra M, Nandy SK, Banik M, Dasgupta R, Basu T (2014) In vitro holdase activity of E. coli small heat-shock proteins IbpA, IbpB and IbpAB: a biophysical study with some unconventional techniques. Protein Pept Lett 21(6):564–571. https://doi.org/10.2174/0929866521666131224094408
Sprague-Piercy MA, Rocha MA, Kwok AO, Martin RW (2021) α-crystallins in the vertebrate eye lens: complex oligomers and molecular chaperoneS. Annu Rev Phys Chem 72:143–163. https://doi.org/10.1146/annurev-physchem-090419-121428
Strózecka J, Chrusciel E, Górna E, Szymanska A, Ziętkiewicz S, Liberek K (2012) Importance of N- and C-terminal regions of IbpA, Escherichia coli small heat shock protein, for chaperone function and oligomerization. J Biol Chem 287:2843–2853. https://doi.org/10.1074/jbc.M111.273847
Sun W, Van Montagu M, Verbruggen N (2002) Small heat shock proteins and stress tolerance in plants. BBA 1577(1):1–9. https://doi.org/10.1016/s0167-4781(02)00417-7
Tikhomirova TS, Selivanova OM, Galzitskaya OV (2017) α-Crystallins are small heat shock proteins: functional and structural properties. Biochemistry 82(2):106–121. https://doi.org/10.1134/s0006297917020031
Treweek TM, Meehan S, Ecroyd H, Carver JA (2015) Small heat-shock proteins: Important players in regulating cellular proteostasis. Cell Mol Life Sci 72:429–451. https://doi.org/10.1007/s00018-014-1754-5
Valdez MM, Clark JI, Wu GJS, Muchowski PJ (2002) Functional similarities between the small heat shock proteins Mycobacterium tuberculosis HSP 16.3 and human alphaB-crystallin. Eur J Biochem 269:1806–1813. https://doi.org/10.1046/j.1432-1033.2002.02812.x
Waldminghaus T, Gaubig LC, Klinkert B, Narberhaus F (2009) The Escherichia coli ibpA thermometer is comprised of stable and unstable structural elements. RNA Biol 6:455–463. https://doi.org/10.4161/rna.6.4.9014
White HE, Orlova EV, Chen S, Wang L, Ignatiou A, Gowen B, Stromer T, Franzmann TM, Haslbeck M, Buchner J, Saibil HR (2006) Multiple distinct assemblies reveal conformational flexibility in the small heat shock protein Hsp26. Structure 14:1197–1204. https://doi.org/10.1016/j.str.2006.05.021
Young JC (2010) Mechanisms of the Hsp70 chaperone system. Biochem Cell Biol = Biochim Biol Cell 88(2):291–300. https://doi.org/10.1139/o09-175
Zhao L, Vecchi G Vendruscolo M, Körner R, Hayer-Hartl M, Hartl FU (2019) The Hsp70 chaperone system stabilizes a thermo-sensitive subproteome in E. coli. Cell Rep 28(5):1335–1345. https://doi.org/10.1016/j.celrep.2019.06.081
Zhao L, Zheng YG, Feng YH, Li MY, Wang GQ, Ma YF (2020) Toxic effects of waterborne lead (Pb) on bioaccumulation, serum biochemistry, oxidative stress and heat shock protein-related genes expression in Channa argus. Chemosphere 261:127714. https://doi.org/10.1016/j.chemosphere.2020.127714
Zheng B, Halperin T, Hruskova-Heidingsfeldova O, Adam Z, Clarke AK (2002) Characterization of chloroplast Clp proteins in Arabidopsis: localization, tissue specificity and stress responses. Physiol Plant 114(1):92–101. https://doi.org/10.1034/j.1399-3054.2002.1140113.x
Zuehlke A, Johnson JL (2010) Hsp90 and co-chaperones twist the functions of diverse client proteins. Biopolymers 93(3):211–217. https://doi.org/10.1002/bip.21292
Żwirowski S, Kłosowska A, Obuchowski I, Nillegoda NB, Piróg A, Ziętkiewicz S, Bukau B, Mogk A, Liberek K (2017) Hsp70 displaces small heat shock proteins from aggregates to initiate protein refolding. EMBO J 36(6):783–796. https://doi.org/10.15252/embj.201593378
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We are indebted to the Department of Science and Technology and Biotechnology (DSTBT), Government of West Bengal, for financial assistance. We further acknowledge the University Grant Commission, Govt. of India, for the ‘Departmental Research Support (II)’ grant under its ‘Special Assistance Programme’, and the Department of Science and Technology, Govt. of India, for its ‘Funds for Improvement of Science and Technology Infrastructure (FIST)’ to our department of Biochemistry and Biophysics.
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Department of Science and Technology and Biotechnology (DSTBT),Gov. of West Bengal,University Grant Commission-SAP (UGC-SAP),Gov. of India),Department of Science and Technology,Gov. of India for FIST,Department of Higher Education,Government of West Bengal,University of Kalyani,West Bengal,India for their fellowship
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Azaharuddin, M., Pal, A., Mitra, S. et al. A review on oligomeric polydispersity and oligomers-dependent holding chaperone activity of the small heat-shock protein IbpB of Escherichia coli. Cell Stress and Chaperones 28, 689–696 (2023). https://doi.org/10.1007/s12192-023-01392-3
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DOI: https://doi.org/10.1007/s12192-023-01392-3