Research Article
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Year 2023, Volume: 2 Issue: 1, 96 - 113, 13.12.2023

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References

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  • [2] Macario a J et al. Stress genes and proteins in the archaea. Microbiology and molecular biology reviews : MMBR, 1999;63(4):923–967. DOI: 10.1128/MMBR.63.4.923-967.1999
  • [3] Haslbeck M, Vierling E. A First Line of Stress Defense: Small Heat Shock Proteins and Their Function in Protein Homeostasis. Journal of Molecular Biology, 2015;427(7):1537–1548. DOI:10.1016/j.jmb.2015.02.002
  • [4] Tedesco B et al. Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases. Frontiers in Molecular Biosciences, 2022;9:1–27. DOI:10.3389/fmolb.2022.842149
  • [5] Roy M, Bhakta K, Ghosh A. Minimal Yet Powerful: The Role of Archaeal Small Heat Shock Proteins in Maintaining Protein Homeostasis. Frontiers in Molecular Biosciences, 2022;9:1–9. DOI:10.3389/fmolb.2022.832160
  • [6] Haslbeck M, Weinkauf S, Buchner J. Small heat shock proteins: Simplicity meets complexity. Journal of Biological Chemistry, 2019;294:2121–2132. DOI:10.1074/jbc.REV118.002809
  • [7] Reinle K, Mogk A, Bukau B. The Diverse Functions of Small Heat Shock Proteins in the Proteostasis Network. Journal of Molecular Biology, 2021;434(1):167–157. DOI:10.1016/j.jmb.2021.167157
  • [8] Mogk A, Ruger-herreros C, Bukau B. Cellular Functions and Mechanisms of Action of Small Heat Shock Proteins. Annual Review of Microbiology, 2019;73:89–110. DOI:10.1146/annurev-micro-020518-115515
  • [9] Hayashi J, Carver JA. The multifaceted nature of αB-crystallin. Cell Stress and Chaperones,2020;25(4):639–654. DOI:10.1007/s12192-020-01098-w
  • [10] Mogk A, Bukau B. Role of sHsps in organizing cytosolic protein aggregation and disaggregation. Cell Stress and Chaperones,2017;22(4):493-502. DOI:10.1007/s12192-017-0762-4
  • [11] Hilario E et al. Crystal structures of xanthomonas small heat shock protein provide a structural basis for an active molecular chaperone oligomer. Journal of Molecular Biology, 2011;408(1):74–86. DOI:10.1007/s12192-017-0762-410.1016/j.jmb.2011.02.004
  • [12] Obuchowski I, Karaś P, Liberek K. The Small Ones Matter—sHsps in the Bacterial Chaperone Network. Frontiers in Molecular Biosciences, 2021;8:1–7. DOI:10.3389/fmolb.2021.666893
  • [13] Hilton GR et al. C-terminal interactions mediate the quaternary dynamics of αB-crystallin. Philosophical Transactions of the Royal Society B: Biological Sciences, 2013;368(1617):1–13. DOI:10.1098/rstb.2011.0405
  • [14] Clark a. R et al. Crystal structure of R120G disease mutant of human αB-crystallin domain dimer shows closure of a groove. Journal of Molecular Biology, 2011;408(1):118–134. DOI:10.1016/j.jmb.2011.02.020
  • [15] Kim M V et al. Structure and properties of K141E mutant of small heat shock protein HSP22 (HspB8, H11) that is expressed in human neuromuscular disorders. Archives of Biochemistry and Biophysics, 2006;454(1):32–41. DOI:10.1016/j.abb.2006.07.014
  • [16] Litt M et al. Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. Human Molecular Genetics, 1998;7(3):471–474. DOI:10.1093/hmg/7.3.471
  • [17] Vicart P et al. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nature Genetics, 1998;20(1):92–95. DOI:10.1038/1765
  • [18] Kasakov AS et al. Effect of mutations in the β5-β7 loop on the structure and properties of human small heat shock protein HSP22 (HspB8, H11). FEBS Journal,2007;274:5628–5642. DOI:10.1111/j.1742-4658.2007.06086.x
  • [19] Quinlan RA et al. Changes in the quaternary structure and function of MjHSP16.5 attributable to deletion of the IXI motif and introduction of the substitution, R107G, in the α-crystallin domain. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 2013;368(1617):20120327. DOI:10.1098/rstb.2012.0327
  • [20] Kocabıyık S, Aygar S. Improvement of protein stability and enzyme recovery under stress conditions by using a small HSP (tpv-HSP 14.3) from Thermoplasma volcanium. Process Biochemistry, 2012;47(11):1676–1683. DOI:10.1016/j.procbio.2011.11.014
  • [21] Kagi JH, Vallee BL. The role of zinc in alcohol dehydrogenase. V. The effect of metal-binding agents on thestructure of the yeast alcohol dehydrogenase molecule. The Journal of Biological Chemistry, 1960;235:3188–3192. PMID: 13750715.
  • [22] Waterhouse AM et al. Jalview Version 2-A multiple sequence alignment editor and analysis workbench. Bioinformatics, 2009;25(9):1189–1191. DOI: 10.1093/bioinformatics/btp033
  • [23] Cheng J, Randall A, Baldi P. Prediction of protein stability changes for single-site mutations using support vector machines. Proteins: Structure, Function and Genetics, 2006;62(4):1125–1132. DOI: 10.1002/prot.20810
  • [24] Bigman LS, Levy Y. Entropic Contributions to Protein Stability. Israel Journal of Chemistry, 2020;60(7):705–712. DOI: 10.1002/ijch.202000032
  • [25] Kim KK, Kim R, Kim SH. Crystal structure of a small heat-shock protein. Nature, 1998;394(6693):595–599. DOI:10.1038/29106
  • [26] Liu L et al. Active-State Structures of a Small Heat-Shock Protein Revealed a Molecular Switch for Chaperone Function. Structure. 2015;23(11):2066–2075. http://dx.doi.org/10.1016/j.str.2015.08.015. DOI:10.1016/j.str.2015.08.015
  • [27] Hanazono Y et al. Structural Studies on the Oligomeric Transition of a Small Heat Shock Protein, StHsp14.0. Journal of Molecular Biology, 2012;422(1):100–108. DOI:10.1016/j.jmb.2012.05.017
  • [28] van Montfort RL et al. Crystal structure and assembly of a eukaryotic small heat shock protein. Nature Structural Biology, 2001;8(12):1025–1030. DOI:10.1038/nsb722
  • [29] Chen J, Shen B. Computational Analysis of Amino Acid Mutation: A Proteome Wide Perspective. Current Proteomics, 2009;6(4):228–234. DOI: 10.2174/157016409789973734
  • [30] Doss CGP, NagaSundaram N. Investigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: A molecular dynamics approach. PLoS ONE, 2012;7(2):1–11. DOI:10.1371/journal.pone.0031677
  • [31] Goldstein RA. Amino-acid interactions in psychrophiles, mesophiles, thermophiles, and hyperthermophiles: Insights from the quasi-chemical approximation. Protein Science, 2007;16(9):1887–1895. DOI:10.1110/ps.072947007
  • [32] Das KP, Surewicz WK. Temperature-induced exposure of hydrophobic surfaces and its effect on the chaperone activity of α-crystallin. FEBS Letters, 1995;369:321–325. DOI: 10.1016/0014-5793(95)00775-5
  • [33] Kim R et al. On the mechanism of chaperone activity of the small heat-shock protein of Methanococcus jannaschii. Proceedings of the National Academy of Sciences of the United States of America, 2003;100(8):8151–8155. DOI: 10.1073/pnas.1032940100
  • [34] Bova MP, Huang Q, Ding L, Horwitz J. Subunit exchange, conformational stability, and chaperone-like function of the small heat shock protein 16.5 from Methanococcus jannaschii. Journal of Biological Chemistry, 2002;277(41):38468–38475. DOI: 10.1074/jbc.M205594200
  • [35] Moutaoufik MT et al. Oligomerization and chaperone-like activity of Drosophila melanogaster small heat shock protein DmHsp27 and three arginine mutants in the alpha-crystallin domain. Cell Stress and Chaperones, 2017;22:455–466. DOI:10.1007/s12192-016-0748-7
  • [36] Santhoshkumar P, Sharma KK. Conserved F84 and P86 residues in αB-crystallin are essential to effectively prevent the aggregation of substrate proteins. Protein Science, 2006;15:2488–2498. DOI: 10.1110/ps.062338206
  • [37] Shroff NP, Bera S, Cherian-Shaw M, Abraham EC. Substituted hydrophobic and hydrophilic residues at methionine-68 influence the chaperone-like function of αB-crystallin. Molecular and Cellular Biochemistry, 2001;220:127–133. DOI: 10.1023/A:1010834107809
  • [38] Zabci S. Therapeutic importance of small heat shock proteins and their interactions with other proteins In: Arıcı Y, Hancı H (ed).Multidisciplinary Approach to Basic and Clinical Science. Ankara:IKSAD International Publishing House; 2023:61-77.[ISBN: 978-625-367-203-4] https://iksadyayinevi.com/home/multidisciplinary-approach-to-basic-and-clinical-science/
  • [39] Mymrikov E V., Seit-Nebi AS, Gusev NB. Large potentials of small heat shock Proteins. Physiological Reviews, 2011;91(4):1123–1159. DOI:10.1152/physrev.00023.2010
  • [40] Muranova LK et al. Small Heat Shock Proteins and Human Neurodegenerative Diseases. Biochemistry, 2019;84(11):1256–1267. DOI: 10.1134/S000629791911004X

Structural and Functional Impacts of the Altered Hydrophobicity in the Dimer Interface of Tpv HSP 14.3

Year 2023, Volume: 2 Issue: 1, 96 - 113, 13.12.2023

Abstract

Small heat shock proteins (sHSPs) are the ATP-independent molecular chaperones that prevent protein aggregation in the cell by forming stable complexes with unfolded and misfolded proteins. Their distinctive structural characteristics are their low molecular weight (from 14 to 43 kDa) and a tripartite domain architecture. The highly conserved Alpha Crystallin Domain (ACD) plays a central role in the dimerization of sHSPs and acts as the structural building block for oligomerization. The point mutations in the ACD of the human sHSPs that interfere with the dimer integrity are linked to several diseases, including cataracts, desmin-related myopathy, cardiomyopathy, and distal hereditary motor neuropathy. In the present study, we investigated the functional and structural implications of amino acid changes at two putative dimer interface residues, L33 and Y34. These residues are located on the β2 strand of Tpv HSP 14.3, which is implicated in ACD dimerization via strand exchange. Effects of the substitutions were evaluated by performing chaperone assays using the client proteins pig heart Citrate Synthase (phCS) and Alcohol Dehydrogenase (ADH) and through in silico molecular bond and structure analyses of the wild type and generated mutant proteins. Our results indicated that an excess amount of WT and the mutant proteins are required to maintain phCS activity to a level comparable to or even higher than the positive control. At a lower substrate/sHSP ratio, the Y34F mutant protected the phCS activity more effectively than the WT and L33S mutant sHSPs. Also, the Y34F mutant sHSP afforded the highest protection of ADH enzyme from heat inactivation. It is likely that increased hydrophobicity by Y34F substitution contributed to the formation of a hydrophobic surface that may capture aggregation-prone substrates. According to molecular bond analysis, the loss of intermolecular hydrophobic interactions between leucine 33 on the β2 strand and tyrosine 77 and isoleucine 78 on the β6 strand can be critical for the reduced structural/thermodynamic stability of the L33S mutant protein.

Thanks

The authors acknowledge METU-BAP for partially supporting this project with grants (TEZ-D-108-2020-10187).

References

  • [1] Hu C et al. Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities. MedComm, 2022;3(3):1–39. DOI:10.1002/mco2.161
  • [2] Macario a J et al. Stress genes and proteins in the archaea. Microbiology and molecular biology reviews : MMBR, 1999;63(4):923–967. DOI: 10.1128/MMBR.63.4.923-967.1999
  • [3] Haslbeck M, Vierling E. A First Line of Stress Defense: Small Heat Shock Proteins and Their Function in Protein Homeostasis. Journal of Molecular Biology, 2015;427(7):1537–1548. DOI:10.1016/j.jmb.2015.02.002
  • [4] Tedesco B et al. Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases. Frontiers in Molecular Biosciences, 2022;9:1–27. DOI:10.3389/fmolb.2022.842149
  • [5] Roy M, Bhakta K, Ghosh A. Minimal Yet Powerful: The Role of Archaeal Small Heat Shock Proteins in Maintaining Protein Homeostasis. Frontiers in Molecular Biosciences, 2022;9:1–9. DOI:10.3389/fmolb.2022.832160
  • [6] Haslbeck M, Weinkauf S, Buchner J. Small heat shock proteins: Simplicity meets complexity. Journal of Biological Chemistry, 2019;294:2121–2132. DOI:10.1074/jbc.REV118.002809
  • [7] Reinle K, Mogk A, Bukau B. The Diverse Functions of Small Heat Shock Proteins in the Proteostasis Network. Journal of Molecular Biology, 2021;434(1):167–157. DOI:10.1016/j.jmb.2021.167157
  • [8] Mogk A, Ruger-herreros C, Bukau B. Cellular Functions and Mechanisms of Action of Small Heat Shock Proteins. Annual Review of Microbiology, 2019;73:89–110. DOI:10.1146/annurev-micro-020518-115515
  • [9] Hayashi J, Carver JA. The multifaceted nature of αB-crystallin. Cell Stress and Chaperones,2020;25(4):639–654. DOI:10.1007/s12192-020-01098-w
  • [10] Mogk A, Bukau B. Role of sHsps in organizing cytosolic protein aggregation and disaggregation. Cell Stress and Chaperones,2017;22(4):493-502. DOI:10.1007/s12192-017-0762-4
  • [11] Hilario E et al. Crystal structures of xanthomonas small heat shock protein provide a structural basis for an active molecular chaperone oligomer. Journal of Molecular Biology, 2011;408(1):74–86. DOI:10.1007/s12192-017-0762-410.1016/j.jmb.2011.02.004
  • [12] Obuchowski I, Karaś P, Liberek K. The Small Ones Matter—sHsps in the Bacterial Chaperone Network. Frontiers in Molecular Biosciences, 2021;8:1–7. DOI:10.3389/fmolb.2021.666893
  • [13] Hilton GR et al. C-terminal interactions mediate the quaternary dynamics of αB-crystallin. Philosophical Transactions of the Royal Society B: Biological Sciences, 2013;368(1617):1–13. DOI:10.1098/rstb.2011.0405
  • [14] Clark a. R et al. Crystal structure of R120G disease mutant of human αB-crystallin domain dimer shows closure of a groove. Journal of Molecular Biology, 2011;408(1):118–134. DOI:10.1016/j.jmb.2011.02.020
  • [15] Kim M V et al. Structure and properties of K141E mutant of small heat shock protein HSP22 (HspB8, H11) that is expressed in human neuromuscular disorders. Archives of Biochemistry and Biophysics, 2006;454(1):32–41. DOI:10.1016/j.abb.2006.07.014
  • [16] Litt M et al. Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. Human Molecular Genetics, 1998;7(3):471–474. DOI:10.1093/hmg/7.3.471
  • [17] Vicart P et al. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nature Genetics, 1998;20(1):92–95. DOI:10.1038/1765
  • [18] Kasakov AS et al. Effect of mutations in the β5-β7 loop on the structure and properties of human small heat shock protein HSP22 (HspB8, H11). FEBS Journal,2007;274:5628–5642. DOI:10.1111/j.1742-4658.2007.06086.x
  • [19] Quinlan RA et al. Changes in the quaternary structure and function of MjHSP16.5 attributable to deletion of the IXI motif and introduction of the substitution, R107G, in the α-crystallin domain. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 2013;368(1617):20120327. DOI:10.1098/rstb.2012.0327
  • [20] Kocabıyık S, Aygar S. Improvement of protein stability and enzyme recovery under stress conditions by using a small HSP (tpv-HSP 14.3) from Thermoplasma volcanium. Process Biochemistry, 2012;47(11):1676–1683. DOI:10.1016/j.procbio.2011.11.014
  • [21] Kagi JH, Vallee BL. The role of zinc in alcohol dehydrogenase. V. The effect of metal-binding agents on thestructure of the yeast alcohol dehydrogenase molecule. The Journal of Biological Chemistry, 1960;235:3188–3192. PMID: 13750715.
  • [22] Waterhouse AM et al. Jalview Version 2-A multiple sequence alignment editor and analysis workbench. Bioinformatics, 2009;25(9):1189–1191. DOI: 10.1093/bioinformatics/btp033
  • [23] Cheng J, Randall A, Baldi P. Prediction of protein stability changes for single-site mutations using support vector machines. Proteins: Structure, Function and Genetics, 2006;62(4):1125–1132. DOI: 10.1002/prot.20810
  • [24] Bigman LS, Levy Y. Entropic Contributions to Protein Stability. Israel Journal of Chemistry, 2020;60(7):705–712. DOI: 10.1002/ijch.202000032
  • [25] Kim KK, Kim R, Kim SH. Crystal structure of a small heat-shock protein. Nature, 1998;394(6693):595–599. DOI:10.1038/29106
  • [26] Liu L et al. Active-State Structures of a Small Heat-Shock Protein Revealed a Molecular Switch for Chaperone Function. Structure. 2015;23(11):2066–2075. http://dx.doi.org/10.1016/j.str.2015.08.015. DOI:10.1016/j.str.2015.08.015
  • [27] Hanazono Y et al. Structural Studies on the Oligomeric Transition of a Small Heat Shock Protein, StHsp14.0. Journal of Molecular Biology, 2012;422(1):100–108. DOI:10.1016/j.jmb.2012.05.017
  • [28] van Montfort RL et al. Crystal structure and assembly of a eukaryotic small heat shock protein. Nature Structural Biology, 2001;8(12):1025–1030. DOI:10.1038/nsb722
  • [29] Chen J, Shen B. Computational Analysis of Amino Acid Mutation: A Proteome Wide Perspective. Current Proteomics, 2009;6(4):228–234. DOI: 10.2174/157016409789973734
  • [30] Doss CGP, NagaSundaram N. Investigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: A molecular dynamics approach. PLoS ONE, 2012;7(2):1–11. DOI:10.1371/journal.pone.0031677
  • [31] Goldstein RA. Amino-acid interactions in psychrophiles, mesophiles, thermophiles, and hyperthermophiles: Insights from the quasi-chemical approximation. Protein Science, 2007;16(9):1887–1895. DOI:10.1110/ps.072947007
  • [32] Das KP, Surewicz WK. Temperature-induced exposure of hydrophobic surfaces and its effect on the chaperone activity of α-crystallin. FEBS Letters, 1995;369:321–325. DOI: 10.1016/0014-5793(95)00775-5
  • [33] Kim R et al. On the mechanism of chaperone activity of the small heat-shock protein of Methanococcus jannaschii. Proceedings of the National Academy of Sciences of the United States of America, 2003;100(8):8151–8155. DOI: 10.1073/pnas.1032940100
  • [34] Bova MP, Huang Q, Ding L, Horwitz J. Subunit exchange, conformational stability, and chaperone-like function of the small heat shock protein 16.5 from Methanococcus jannaschii. Journal of Biological Chemistry, 2002;277(41):38468–38475. DOI: 10.1074/jbc.M205594200
  • [35] Moutaoufik MT et al. Oligomerization and chaperone-like activity of Drosophila melanogaster small heat shock protein DmHsp27 and three arginine mutants in the alpha-crystallin domain. Cell Stress and Chaperones, 2017;22:455–466. DOI:10.1007/s12192-016-0748-7
  • [36] Santhoshkumar P, Sharma KK. Conserved F84 and P86 residues in αB-crystallin are essential to effectively prevent the aggregation of substrate proteins. Protein Science, 2006;15:2488–2498. DOI: 10.1110/ps.062338206
  • [37] Shroff NP, Bera S, Cherian-Shaw M, Abraham EC. Substituted hydrophobic and hydrophilic residues at methionine-68 influence the chaperone-like function of αB-crystallin. Molecular and Cellular Biochemistry, 2001;220:127–133. DOI: 10.1023/A:1010834107809
  • [38] Zabci S. Therapeutic importance of small heat shock proteins and their interactions with other proteins In: Arıcı Y, Hancı H (ed).Multidisciplinary Approach to Basic and Clinical Science. Ankara:IKSAD International Publishing House; 2023:61-77.[ISBN: 978-625-367-203-4] https://iksadyayinevi.com/home/multidisciplinary-approach-to-basic-and-clinical-science/
  • [39] Mymrikov E V., Seit-Nebi AS, Gusev NB. Large potentials of small heat shock Proteins. Physiological Reviews, 2011;91(4):1123–1159. DOI:10.1152/physrev.00023.2010
  • [40] Muranova LK et al. Small Heat Shock Proteins and Human Neurodegenerative Diseases. Biochemistry, 2019;84(11):1256–1267. DOI: 10.1134/S000629791911004X
There are 40 citations in total.

Details

Primary Language English
Subjects Structural Biology, Gene Expression, Molecular Genetics, Microbial Genetics
Journal Section Research Articles
Authors

Sema Zabcı 0000-0002-8886-0077

Azra Rafiq This is me 0000-0003-1760-0136

Semra Kocabıyık 0000-0003-2699-3058

Publication Date December 13, 2023
Submission Date November 23, 2023
Acceptance Date December 2, 2023
Published in Issue Year 2023 Volume: 2 Issue: 1

Cite

EndNote Zabcı S, Rafiq A, Kocabıyık S (December 1, 2023) Structural and Functional Impacts of the Altered Hydrophobicity in the Dimer Interface of Tpv HSP 14.3. Anatolian Journal of Pharmaceutical Sciences 2 1 96–113.

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