DOI: 10.1073/pnas.98.3.914. Subunit interactions influence the biochemical and biological properties of Hsp104

Subunit interactions influence the biochemical and biological properties of Hsp104

10.1073/pnas.98.3.914

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Point mutations in either of the two nucleotide-binding domains (NBD) of Hsp104 (NBD1 and NBD2) eliminate its thermotolerance function in vivo . In vitro , NBD1 mutations virtually eliminate ATP hydrolysis with little effect on hexamerization; analogous NBD2 mutations reduce ATPase activity and severely impair hexamerization. We report that high protein concentrations overcome the assembly defects of NBD2 mutants and increase ATP hydrolysis severalfold, changing V max with little effect on K m . In a complementary fashion, the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate inhibits hexamerization of wild-type (WT) Hsp104, lowering V max with little effect on K m . ATP hydrolysis exhibits a Hill coefficient between 1.5 and 2, indicating that it is influenced by cooperative subunit interactions. To further analyze the effects of subunit interactions on Hsp104, we assessed the effects of mutant Hsp104 proteins on WT Hsp104 activities. An NBD1 mutant that hexamerizes but does not hydrolyze ATP reduces the ATPase activity of WT Hsp104 in vitro . In vivo , this mutant is not toxic but specifically inhibits the thermotolerance function of WT Hsp104. Thus, interactions between subunits influence the ATPase activity of Hsp104, play a vital role in its biological functions, and provide a mechanism for conditionally inactivating Hsp104 function in vivo .

Bibliography

Schirmer, E. C., Ware, D. M., Queitsch, C., Kowal, A. S., & Lindquist, S. L. (2001). Subunit interactions influence the biochemical and biological properties of Hsp104. Proceedings of the National Academy of Sciences, 98(3), 914â919.

Authors 5

Eric C. Schirmer (first)
Danielle M. Ware (additional)
Christine Queitsch (additional)
Anthony S. Kowal (additional)
Susan L. Lindquist (additional)

References 30 Referenced 58

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S Lindquist, E C Schirmer Molecular Chaperones and Folding Catalysts: Regulation, Cellular Function and Mechanisms, ed B Bukau (Harwood, Amsterdam), pp. 347–380 (1999). / Molecular Chaperones and Folding Catalysts: Regulation, Cellular Function and Mechanisms by Lindquist S (1999)
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Dates

Type	When
Created	13 years, 1 month ago (July 26, 2012, 7:06 p.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:26 p.m.)
Indexed	11 months, 2 weeks ago (Sept. 13, 2024, 12:43 p.m.)
Issued	24 years, 7 months ago (Jan. 23, 2001)
Published	24 years, 7 months ago (Jan. 23, 2001)
Published Online	24 years, 7 months ago (Jan. 23, 2001)
Published Print	24 years, 6 months ago (Jan. 30, 2001)

Funders 0

None

BibTeX

@article{Schirmer_2001, title={Subunit interactions influence the biochemical and biological properties of Hsp104}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.98.3.914}, DOI={10.1073/pnas.98.3.914}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Schirmer, Eric C. and Ware, Danielle M. and Queitsch, Christine and Kowal, Anthony S. and Lindquist, Susan L.}, year={2001}, month=jan, pages={914–919} }

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  "abstract": "<jats:p>\n            Point mutations in either of the two nucleotide-binding domains\n (NBD) of Hsp104 (NBD1 and NBD2) eliminate its thermotolerance function\n            <jats:italic>in vivo</jats:italic>\n            .\n            <jats:italic>In vitro</jats:italic>\n            , NBD1 mutations\n virtually eliminate ATP hydrolysis with little effect on\n hexamerization; analogous NBD2 mutations reduce ATPase activity and\n severely impair hexamerization. We report that high protein\n concentrations overcome the assembly defects of NBD2 mutants and\n increase ATP hydrolysis severalfold, changing\n            <jats:italic>V</jats:italic>\n            <jats:sub>max</jats:sub>\n            with little effect on\n            <jats:italic>K</jats:italic>\n            <jats:sub>m</jats:sub>\n            . In a complementary fashion, the\n detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate\n inhibits hexamerization of wild-type (WT) Hsp104, lowering\n            <jats:italic>V</jats:italic>\n            <jats:sub>max</jats:sub>\n            with little effect on\n            <jats:italic>K</jats:italic>\n            <jats:sub>m</jats:sub>\n            . ATP hydrolysis exhibits a Hill\n coefficient between 1.5 and 2, indicating that it is influenced by\n cooperative subunit interactions. To further analyze the effects of\n subunit interactions on Hsp104, we assessed the effects of mutant\n Hsp104 proteins on WT Hsp104 activities. An NBD1 mutant that\n hexamerizes but does not hydrolyze ATP reduces the ATPase activity of\n WT Hsp104\n            <jats:italic>in vitro</jats:italic>\n            .\n            <jats:italic>In vivo</jats:italic>\n            , this mutant\n is not toxic but specifically inhibits the thermotolerance function of\n WT Hsp104. Thus, interactions between subunits influence the ATPase\n activity of Hsp104, play a vital role in its biological functions, and\n provide a mechanism for conditionally inactivating Hsp104 function\n            <jats:italic>in vivo</jats:italic>\n            .\n          </jats:p>",
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