DOI: 10.1073/pnas.2235804100. Distinct peptide signals in the UmuD and UmuD′ subunits of UmuD/D′ mediate tethering and substrate processing by the ClpXP protease

Distinct peptide signals in the UmuD and UmuD′ subunits of UmuD/D′ mediate tethering and substrate processing by the ClpXP protease

10.1073/pnas.2235804100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The Escherichia coli UmuD′ protein is a component of DNA polymerase V, an error-prone polymerase that carries out translesion synthesis on damaged DNA templates. The intracellular concentration of UmuD′ is strictly controlled by regulated transcription, by posttranslational processing of UmuD to UmuD′, and by ClpXP degradation. UmuD′ is a substrate for the ClpXP protease but must form a heterodimer with its unabbreviated precursor, UmuD, for efficient degradation to occur. Here, we show that UmuD functions as a UmuD′ delivery protein for ClpXP. UmuD can also deliver a UmuD partner for degradation. UmuD resembles SspB, a well-characterized substrate-delivery protein for ClpX, in that both proteins use related peptide motifs to bind to the N-terminal domain of ClpX, thereby tethering substrate complexes to ClpXP. The combined use of a weak substrate recognition signal and a delivery factor that tethers the substrate to the protease allows regulated proteolysis of UmuD/D′ in the cell. Dual recognition strategies of this type may be a relatively common feature of intracellular protein turnover.

Bibliography

Neher, S. B., Sauer, R. T., & Baker, T. A. (2003). Distinct peptide signals in the UmuD and UmuDâ² subunits of UmuD/Dâ² mediate tethering and substrate processing by the ClpXP protease. Proceedings of the National Academy of Sciences, 100(23), 13219â13224.

Authors 3

Saskia B. Neher (first)
Robert T. Sauer (additional)
Tania A. Baker (additional)

References 38 Referenced 89

Dates

Type	When
Created	21 years, 9 months ago (Nov. 16, 2003, 3:42 p.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 7:42 a.m.)
Indexed	1 month, 2 weeks ago (July 11, 2025, 6:27 a.m.)
Issued	21 years, 10 months ago (Oct. 31, 2003)
Published	21 years, 10 months ago (Oct. 31, 2003)
Published Online	21 years, 10 months ago (Oct. 31, 2003)
Published Print	21 years, 9 months ago (Nov. 11, 2003)

Funders 0

None

BibTeX

@article{Neher_2003, title={Distinct peptide signals in the UmuD and UmuD′ subunits of UmuD/D′ mediate tethering and substrate processing by the ClpXP protease}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.2235804100}, DOI={10.1073/pnas.2235804100}, number={23}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Neher, Saskia B. and Sauer, Robert T. and Baker, Tania A.}, year={2003}, month=oct, pages={13219–13224} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        11
      ]
    ],
    "date-time": "2025-07-11T10:27:05Z",
    "timestamp": 1752229625794
  },
  "reference-count": 38,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "23",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2003,
        11,
        11
      ]
    ]
  },
  "abstract": "<jats:p>\n            The\n            <jats:italic>Escherichia coli</jats:italic>\n            UmuD\u2032 protein is a component of DNA polymerase V, an error-prone polymerase that carries out translesion synthesis on damaged DNA templates. The intracellular concentration of UmuD\u2032 is strictly controlled by regulated transcription, by posttranslational processing of UmuD to UmuD\u2032, and by ClpXP degradation. UmuD\u2032 is a substrate for the ClpXP protease but must form a heterodimer with its unabbreviated precursor, UmuD, for efficient degradation to occur. Here, we show that UmuD functions as a UmuD\u2032 delivery protein for ClpXP. UmuD can also deliver a UmuD partner for degradation. UmuD resembles SspB, a well-characterized substrate-delivery protein for ClpX, in that both proteins use related peptide motifs to bind to the N-terminal domain of ClpX, thereby tethering substrate complexes to ClpXP. The combined use of a weak substrate recognition signal and a delivery factor that tethers the substrate to the protease allows regulated proteolysis of UmuD/D\u2032 in the cell. Dual recognition strategies of this type may be a relatively common feature of intracellular protein turnover.\n          </jats:p>",
  "DOI": "10.1073/pnas.2235804100",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2003,
        11,
        16
      ]
    ],
    "date-time": "2003-11-16T20:42:47Z",
    "timestamp": 1069015367000
  },
  "page": "13219-13224",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 89,
  "title": "Distinct peptide signals in the UmuD and UmuD\u2032 subunits of UmuD/D\u2032 mediate tethering and substrate processing by the ClpXP protease",
  "prefix": "10.1073",
  "volume": "100",
  "author": [
    {
      "given": "Saskia B.",
      "family": "Neher",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Robert T.",
      "family": "Sauer",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Tania A.",
      "family": "Baker",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2003,
        10,
        31
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jb.175.1.53-63.1993"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JB.185.1.115-125.2003"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)41573-6"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(19)38378-4"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1097-2765(00)80243-9"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.97.16.8898"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80431-6"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.20.13999"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1097-2765(03)00060-1"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.12.9.1338"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M209352200"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.1078003"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(03)00612-3"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.16.9322"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.271.5251.990"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1097-2765(01)00307-0"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.864401"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.289.5488.2354"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/cdg411"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1097-2765(03)00272-7"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1074-5521(02)00268-5"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.85.6.1811"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.85.6.1806"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.87.18.7190"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/19.19.5251"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.molcel.2003.08.012"
    },
    {
      "key": "e_1_3_2_27_2",
      "unstructured": "Wojtyra U. A. Thibault G. Tuite A. & Houry W. A. (2003) J. Biol. Chem. 10.1074/jbc.M307825200."
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi961375t"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1568-7864(01)00006-4"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jb.176.16.4825-4837.1994"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nsb1297-979"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/20.15.4287"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M103489200"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/20.12.3092"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0022-2836(02)01042-2"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.96.16.8919"
    },
    {
      "key": "e_1_3_2_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.95.17.9755"
    },
    {
      "key": "e_1_3_2_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.12.24.3889"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.2235804100",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        13
      ]
    ],
    "date-time": "2022-04-13T11:42:43Z",
    "timestamp": 1649850163000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.2235804100"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2003,
        10,
        31
      ]
    ]
  },
  "references-count": 38,
  "journal-issue": {
    "issue": "23",
    "published-print": {
      "date-parts": [
        [
          2003,
          11,
          11
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.2235804100"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.2235804100",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2003,
        10,
        31
      ]
    ]
  },
  "assertion": [
    {
      "value": "2003-10-31",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}