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LanCLs add glutathione to dehydroamino acids generated at phosphorylated sites in the proteome.
Lai, Kuan-Yu; Galan, Sébastien R G; Zeng, Yibo; Zhou, Tianhui Hina; He, Chang; Raj, Ritu; Riedl, Jitka; Liu, Shi; Chooi, K Phin; Garg, Neha; Zeng, Min; Jones, Lyn H; Hutchings, Graham J; Mohammed, Shabaz; Nair, Satish K; Chen, Jie; Davis, Benjamin G; van der Donk, Wilfred A.
Afiliação
  • Lai KY; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • Galan SRG; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield, Oxford OX1 3TA, UK.
  • Zeng Y; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield, Oxford OX1 3TA, UK; UK Catalysis Hub, Research Complex at Harwell, Rutherford Appleton Laboratory, Harwell, Oxford OX11 0FA, UK; The Rosalind Franklin Institute, Oxfordshire OX11 0FA, UK.
  • Zhou TH; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • He C; Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • Raj R; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield, Oxford OX1 3TA, UK.
  • Riedl J; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield, Oxford OX1 3TA, UK.
  • Liu S; Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • Chooi KP; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield, Oxford OX1 3TA, UK.
  • Garg N; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • Zeng M; Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • Jones LH; Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02115, USA.
  • Hutchings GJ; UK Catalysis Hub, Research Complex at Harwell, Rutherford Appleton Laboratory, Harwell, Oxford OX11 0FA, UK; Cardiff Catalysis Institute, School of Chemistry, Cardiff University, Cardiff CF10 3AT, UK.
  • Mohammed S; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield, Oxford OX1 3TA, UK; The Rosalind Franklin Institute, Oxfordshire OX11 0FA, UK.
  • Nair SK; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • Chen J; Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: jiechen@life.illinois.edu.
  • Davis BG; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield, Oxford OX1 3TA, UK; The Rosalind Franklin Institute, Oxfordshire OX11 0FA, UK. Electronic address: ben.davis@chem.ox.ac.uk.
  • van der Donk WA; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: vddonk@illinois.edu.
Cell ; 184(10): 2680-2695.e26, 2021 05 13.
Article em En | MEDLINE | ID: mdl-33932340
ABSTRACT
Enzyme-mediated damage repair or mitigation, while common for nucleic acids, is rare for proteins. Examples of protein damage are elimination of phosphorylated Ser/Thr to dehydroalanine/dehydrobutyrine (Dha/Dhb) in pathogenesis and aging. Bacterial LanC enzymes use Dha/Dhb to form carbon-sulfur linkages in antimicrobial peptides, but the functions of eukaryotic LanC-like (LanCL) counterparts are unknown. We show that LanCLs catalyze the addition of glutathione to Dha/Dhb in proteins, driving irreversible C-glutathionylation. Chemo-enzymatic methods were developed to site-selectively incorporate Dha/Dhb at phospho-regulated sites in kinases. In human MAPK-MEK1, such "elimination damage" generated aberrantly activated kinases, which were deactivated by LanCL-mediated C-glutathionylation. Surveys of endogenous proteins bearing damage from elimination (the eliminylome) also suggest it is a source of electrophilic reactivity. LanCLs thus remove these reactive electrophiles and their potentially dysregulatory effects from the proteome. As knockout of LanCL in mice can result in premature death, repair of this kind of protein damage appears important physiologically.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / Proteínas de Ligação a Fosfato / Receptores Acoplados a Proteínas G / Alanina / Aminobutiratos / Proteínas de Membrana Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / Proteínas de Ligação a Fosfato / Receptores Acoplados a Proteínas G / Alanina / Aminobutiratos / Proteínas de Membrana Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article