Human metallothioneins 2 and 3 differentially affect amyloid-beta binding by transthyretin

The FEBS Journal
Ana MartinhoCecília R A Santos

Abstract

Transthyretin (TTR), an amyloid-beta (Abeta) scavenger protein, and metallothioneins 2 and 3 (MT2 and MT3), low molecular weight metal-binding proteins, have recognized impacts in Abeta metabolism. Because TTR binds MT2, an ubiquitous isoform of the MTs, we investigated whether it also interacts with MT3, an isoform of the MTs predominantly expressed in the brain, and studied the role of MT2 and MT3 in human TTR-Abeta binding. The TTR-MT3 interaction was characterized by yeast two-hybrid assays, saturation-binding assays, co-immunolocalization and co-immunoprecipitation. The effect of MT2 and MT3 on TTR-Abeta binding was assessed by competition-binding assays. The results obtained clearly demonstrate that TTR interacts with MT3 with a K(d) of 373.7 +/- 60.2 nm. Competition-binding assays demonstrated that MT2 diminishes TTR-Abeta binding, whereas MT3 has the opposite effect. In addition to identifying a novel ligand for TTR that improves human TTR-Abeta binding, the present study highlights the need to clarify whether the effects of MT2 and MT3 in human TTR-Abeta binding observed in vitro have a relevant impact on Abeta deposition in animal models of Alzheimer's disease.

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Citations

Jul 17, 2012·Chemical Reviews·Kasper P Kepp
Jul 7, 2012·Cellular and Molecular Life Sciences : CMLS·Yasmina MansoJuan Hidalgo
Jun 17, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Yasmina MansoJuan Hidalgo
Jul 23, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Adrian K WestRoger S Chung
Mar 13, 2012·Journal of Neurochemistry·Jong-Heon KimKyoungho Suk
Dec 2, 2011·IUBMB Life·Cecília R A SantosIsabel Gonçalves
Mar 1, 2016·Journal of Alzheimer's Disease : JAD·Pavlína AdamVojtěch Adam
Aug 23, 2016·Neurobiology of Disease·Fernanda MarquesJoana Almeida Palha
Sep 16, 2016·Journal of Neuroendocrinology·A C DuarteC R A Santos
Dec 19, 2017·Frontiers in Neurology·W Frank PeacockFrederick K Korley
Jan 8, 2013·Molecular and Cellular Biochemistry·A MartinhoC R Santos
Dec 2, 2020·International Journal of Molecular Sciences·Natalia Zaręba, Marta Kepinska
Aug 10, 2020·Experimental Cell Research·Christoph NiemietzAndree Zibert
Mar 10, 2021·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Kiyoshi Yamauchi
Mar 1, 2017·General and Comparative Endocrinology·Shunsuke SuzukiKiyoshi Yamauchi

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