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cc-by-nc-nd (c) Dallinger, Reinhard et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/229620

Experimental recombining of repetitive motifs leads to large functional metallothioneins and demonstrates their modular evolvability potential.

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Protein modularity is acknowledged for promoting the emergence of new protein variants via domain rearrangements. Metallothioneins (MTs) offer an excellent model system for experimentally examining the consequences of domain rearrangements due to the possibility to assess the functional properties of native and artificially created variants using spectroscopic methods and metal tolerance assays. In this study, we have investigated the functional properties of AbiMT4 from the snail Alinda biplicata (Gastropoda, Mollusca), a large MT comprising 10 putative β domains (β39β1), alongside four artificially designed variants differing in domain number, type, or order. Our findings reveal that AbiMT4 is a cadmium-selective protein with a high metal-binding capacity, characterized by structurally and functionally independent domains repeated in tandem along the protein. Our results indicate that due to its modular organization, AbiMT4 remains functional even when the number, type, and order of the domains are significantly altered. Furthermore, we demonstrate that the metal-binding properties of AbiMT4 are not dictated by the overall architecture of the protein but primarily arise from the properties of each individual domain. Using MTs as example, this work provides empirical evidence that domain rearrangements are an effective strategy for exploring new viable sequences and creating novel protein variants subject to adaptive selection. Thus, our study highlights the importance of the modular structure of proteins, as increasing their functional flexibility enhances their evolvability. Additionally, our work demonstrates a simple way to design and model new proteins for predefined functions.

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DALLINGER, Reinhard, et al. Experimental recombining of repetitive motifs leads to large functional metallothioneins and demonstrates their modular evolvability potential. Protein Science. 2024. Vol. 34, num. 1, pags. e5247. ISSN 0961-8368. [consulted: 25 of May of 2026]. Available at: https://hdl.handle.net/2445/229620

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