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HSP70-binding motif...
HSP70-binding motifs function as protein quality control degrons
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Abildgaard, Amanda B. (författare)
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Voutsinos, Vasileios (författare)
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Petersen, Søren D. (författare)
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Larsen, Fia B. (författare)
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Kampmeyer, Caroline (författare)
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Johansson, Kristoffer E. (författare)
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Stein, Amelie (författare)
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Ravid, Tommer (författare)
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- Andréasson, Claes, 1976- (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden
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Jensen, Michael K. (författare)
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Lindorff-Larsen, Kresten (författare)
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Hartmann-Petersen, Rasmus (författare)
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(creator_code:org_t)
- 2023-01-07
- 2023
- Engelska.
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 80:1
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and thus protect cells against the accumulation of potentially toxic non-native proteins. Studies have shown that PQC degrons are hydrophobic and rarely contain negatively charged residues, features which are shared with chaperone-binding regions. Here we explore the notion that chaperone-binding regions may function as PQC degrons. When directly tested, we found that a canonical Hsp70-binding motif (the APPY peptide) functioned as a dose-dependent PQC degron both in yeast and in human cells. In yeast, Hsp70, Hsp110, Fes1, and the E3 Ubr1 target the APPY degron. Screening revealed that the sequence space within the chaperone-binding region of APPY that is compatible with degron function is vast. We find that the number of exposed Hsp70-binding sites in the yeast proteome correlates with a reduced protein abundance and half-life. Our results suggest that when protein folding fails, chaperone-binding sites may operate as PQC degrons, and that the sequence properties leading to PQC-linked degradation therefore overlap with those of chaperone binding.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- Protein unfolding
- Protein degradation
- Proteasome
- Protein stability
- Protein quality control
- Chaperone
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Abildgaard, Aman ...
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Voutsinos, Vasil ...
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Petersen, Søren ...
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Larsen, Fia B.
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Kampmeyer, Carol ...
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Johansson, Krist ...
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visa fler...
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Stein, Amelie
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Ravid, Tommer
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Andréasson, Clae ...
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Jensen, Michael ...
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Lindorff-Larsen, ...
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Hartmann-Peterse ...
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
- Artiklar i publikationen
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Cellular and Mol ...
- Av lärosätet
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Stockholms universitet