DOI: 10.1073/pnas.0910392106. Degrons in protein substrates program the speed and operating efficiency of the AAA+ Lon proteolytic machine

Degrons in protein substrates program the speed and operating efficiency of the AAA+ Lon proteolytic machine

10.1073/pnas.0910392106

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

AAA+ proteases are ATP-fueled machines that bind protein substrates via a degradation tag, unfold the molecule if necessary, and then translocate the polypeptide into a chamber for proteolysis. Tag recognition is normally viewed as a passive reaction. By contrast, for the AAA+ Lon protease, we show that degron tags are also regulatory elements that determine protease activity levels. Indeed, different tags fused to the same protein change degradation speeds and energetic efficiencies by 10-fold or more. Degron binding to multiple sites in the Lon hexamer appears to differentially stabilize specific enzyme conformations, including one with high protease and low ATPase activity, and results in positively cooperative degradation. These allosteric mechanisms allow Lon to operate in either a fast or slow proteolysis mode, according to specific physiological needs, and may help maximize degradation of misfolded proteins following stress-induced denaturation.

Bibliography

Gur, E., & Sauer, R. T. (2009). Degrons in protein substrates program the speed and operating efficiency of the AAA+ Lon proteolytic machine. Proceedings of the National Academy of Sciences, 106(44), 18503â18508.

Authors 2

Eyal Gur (first)
Robert T. Sauer (additional)

References 31 Referenced 75

10.1146/annurev.genet.30.1.465
10.1016/j.tibs.2006.10.006
10.1016/j.cell.2004.09.020
10.1016/j.resmic.2006.05.004
10.1196/annals.1404.015
10.1073/pnas.78.8.4931
SG Roudiak, TE Shrader, Functional role of the N-terminal region of the Lon protease from. Mycobacterium smegmatis Biochemistry 37, 11255–11263 (1998). / Mycobacterium smegmatis Biochemistry / Functional role of the N-terminal region of the Lon protease from by Roudiak SG (1998)
10.1110/ps.052069306
10.1101/gad.1670908
10.1101/gad.12.24.3889
10.1016/j.jmb.2005.12.088
10.1128/JB.00860-07
10.1073/pnas.0808802105
10.1126/science.2938257
10.1074/jbc.273.1.524
Y Ishii, et al., Regulatory role of C-terminal residues of SulA in its degradation by Lon protease in. Escherichia coli J Biochem 127, 837–844 (2000). / Escherichia coli J Biochem / Regulatory role of C-terminal residues of SulA in its degradation by Lon protease in by Ishii Y (2000)
10.1042/bj3580473
10.1016/S0092-8674(03)00612-3
10.1073/pnas.0409634102
10.1016/S0022-2836(65)80285-6
10.1101/SQB.1963.028.01.065
10.1016/S0021-9258(18)99592-X
10.1016/j.cell.2005.04.012
10.1016/j.molcel.2008.02.002
10.1021/bi701649b
10.1021/bi0255470
10.1073/pnas.96.11.6064
10.1073/pnas.69.2.422
10.1101/gad.12.9.1338
10.1016/0076-6879(88)56014-7
IH Segel Enzyme kinetics: Behavior and analysis of rapid equilibrium and steady-state enzyme systems. (John Wiley & Sons Inc. New York 1975).

Dates

Type	When
Created	15 years, 10 months ago (Oct. 19, 2009, 9:44 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 7:09 p.m.)
Indexed	1 month, 3 weeks ago (July 2, 2025, 2:33 p.m.)
Issued	15 years, 9 months ago (Nov. 3, 2009)
Published	15 years, 9 months ago (Nov. 3, 2009)
Published Online	15 years, 9 months ago (Nov. 3, 2009)
Published Print	15 years, 9 months ago (Nov. 3, 2009)

Funders 0

None

BibTeX

@article{Gur_2009, title={Degrons in protein substrates program the speed and operating efficiency of the AAA+ Lon proteolytic machine}, volume={106}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0910392106}, DOI={10.1073/pnas.0910392106}, number={44}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Gur, Eyal and Sauer, Robert T.}, year={2009}, month=nov, pages={18503–18508} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        2
      ]
    ],
    "date-time": "2025-07-02T18:33:49Z",
    "timestamp": 1751481229690
  },
  "reference-count": 31,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "44",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2009,
        11,
        3
      ]
    ]
  },
  "abstract": "<jats:p>AAA+ proteases are ATP-fueled machines that bind protein substrates via a degradation tag, unfold the molecule if necessary, and then translocate the polypeptide into a chamber for proteolysis. Tag recognition is normally viewed as a passive reaction. By contrast, for the AAA+ Lon protease, we show that degron tags are also regulatory elements that determine protease activity levels. Indeed, different tags fused to the same protein change degradation speeds and energetic efficiencies by 10-fold or more. Degron binding to multiple sites in the Lon hexamer appears to differentially stabilize specific enzyme conformations, including one with high protease and low ATPase activity, and results in positively cooperative degradation. These allosteric mechanisms allow Lon to operate in either a fast or slow proteolysis mode, according to specific physiological needs, and may help maximize degradation of misfolded proteins following stress-induced denaturation.</jats:p>",
  "DOI": "10.1073/pnas.0910392106",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2009,
        10,
        20
      ]
    ],
    "date-time": "2009-10-20T01:44:12Z",
    "timestamp": 1256003052000
  },
  "page": "18503-18508",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 75,
  "title": "Degrons in protein substrates program the speed and operating efficiency of the AAA+ Lon proteolytic machine",
  "prefix": "10.1073",
  "volume": "106",
  "author": [
    {
      "given": "Eyal",
      "family": "Gur",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Robert T.",
      "family": "Sauer",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2009,
        11,
        3
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_3_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.genet.30.1.465"
    },
    {
      "key": "e_1_3_3_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.tibs.2006.10.006"
    },
    {
      "key": "e_1_3_3_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.cell.2004.09.020"
    },
    {
      "key": "e_1_3_3_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.resmic.2006.05.004"
    },
    {
      "key": "e_1_3_3_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1196/annals.1404.015"
    },
    {
      "key": "e_1_3_3_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.78.8.4931"
    },
    {
      "key": "e_1_3_3_7_2",
      "first-page": "11255",
      "article-title": "Functional role of the N-terminal region of the Lon protease from",
      "volume": "37",
      "author": "Roudiak SG",
      "year": "1998",
      "unstructured": "SG Roudiak, TE Shrader, Functional role of the N-terminal region of the Lon protease from. Mycobacterium smegmatis Biochemistry 37, 11255\u201311263 (1998).",
      "journal-title": "Mycobacterium smegmatis Biochemistry"
    },
    {
      "key": "e_1_3_3_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1110/ps.052069306"
    },
    {
      "key": "e_1_3_3_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.1670908"
    },
    {
      "key": "e_1_3_3_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.12.24.3889"
    },
    {
      "key": "e_1_3_3_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.jmb.2005.12.088"
    },
    {
      "key": "e_1_3_3_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JB.00860-07"
    },
    {
      "key": "e_1_3_3_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0808802105"
    },
    {
      "key": "e_1_3_3_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2938257"
    },
    {
      "key": "e_1_3_3_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.273.1.524"
    },
    {
      "key": "e_1_3_3_16_2",
      "first-page": "837",
      "article-title": "Regulatory role of C-terminal residues of SulA in its degradation by Lon protease in",
      "volume": "127",
      "author": "Ishii Y",
      "year": "2000",
      "unstructured": "Y Ishii, et al., Regulatory role of C-terminal residues of SulA in its degradation by Lon protease in. Escherichia coli J Biochem 127, 837\u2013844 (2000).",
      "journal-title": "Escherichia coli J Biochem"
    },
    {
      "key": "e_1_3_3_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj3580473"
    },
    {
      "key": "e_1_3_3_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(03)00612-3"
    },
    {
      "key": "e_1_3_3_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0409634102"
    },
    {
      "key": "e_1_3_3_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0022-2836(65)80285-6"
    },
    {
      "key": "e_1_3_3_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/SQB.1963.028.01.065"
    },
    {
      "key": "e_1_3_3_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)99592-X"
    },
    {
      "key": "e_1_3_3_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.cell.2005.04.012"
    },
    {
      "key": "e_1_3_3_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.molcel.2008.02.002"
    },
    {
      "key": "e_1_3_3_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi701649b"
    },
    {
      "key": "e_1_3_3_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi0255470"
    },
    {
      "key": "e_1_3_3_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.96.11.6064"
    },
    {
      "key": "e_1_3_3_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.69.2.422"
    },
    {
      "key": "e_1_3_3_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.12.9.1338"
    },
    {
      "key": "e_1_3_3_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0076-6879(88)56014-7"
    },
    {
      "key": "e_1_3_3_31_2",
      "unstructured": "IH Segel Enzyme kinetics: Behavior and analysis of rapid equilibrium and steady-state enzyme systems.  (John Wiley & Sons Inc. New York 1975)."
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.0910392106",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        12
      ]
    ],
    "date-time": "2022-04-12T23:09:17Z",
    "timestamp": 1649804957000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.0910392106"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2009,
        11,
        3
      ]
    ]
  },
  "references-count": 31,
  "journal-issue": {
    "issue": "44",
    "published-print": {
      "date-parts": [
        [
          2009,
          11,
          3
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.0910392106"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.0910392106",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2009,
        11,
        3
      ]
    ]
  },
  "assertion": [
    {
      "value": "2009-08-18",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2009-11-03",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}