Metallothionein-protein interactions

Sílvia Atrian, Mercè Capdevila

Research output: Contribution to journalReview articleResearchpeer-review

29 Citations (Scopus)

Abstract

Metallothioneins (MTs) are a family of universal, small proteins, sharing a high cysteine content and an optimal capacity for metal ion coordination. They take part in a plethora of metal ion-related events (from detoxification to homeostasis, storage, and delivery), in a wide range of stress responses, and in different pathological processes (tumorigenesis, neurodegeneration, and inflammation). The information on both intracellular and extracellular interactions of MTs with other proteins is here comprehensively reviewed. In mammalian kidney, MT1/ MT2 interact with megalin and related receptors, and with the transporter transthyretin. Most of the mammalian MT partners identified concern interactions with central nervous system (mainly brain) proteins, both through physical contact or metal exchange reactions. Physical interactions mainly involve neuronal secretion multimers. Regarding metal swap events, brain MT3 appears to control the metal ion load in peptides whose aggregation leads to neurodegenerative disorders, such as A β peptide, α -synuclein, and prion proteins (Alzheimer ' s and Parkinson ' s diseases, and spongiform encephalopathies, respectively). Interaction with ferritin and bovine serum albumin are also documented. The intercourse of MTs with zinc-dependent enzymes and transcription factors is capable to activate/ deactivate them, thus conferring MTs the role of metabolic and gene expression regulators. As some of these proteins are involved in cell cycle and proliferation control (p53, nuclear factor κ B, and PKC μ ), they are considered in the context of oncogenesis and tumor progression. Only one non-mammalian MT interaction, involving Drosophila MtnA and MtnB major isoforms and peroxiredoxins, has been reported. The prospective use for biomedical applications of the MT-interaction information is finally discussed. © 2013 by Walter de Gruyter Berlin Boston.
Original languageEnglish
Pages (from-to)143-160
JournalBiomolecular Concepts
Volume4
Issue number2
DOIs
Publication statusPublished - 1 Apr 2013

Keywords

  • CNS metal ions
  • Metal ions and cancer
  • Metallothionein
  • Neurodegenerative disorders
  • Protein-protein interaction

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