Design of a site selective heterochromic bimetallic lanthanide coiled coil with nanometre-scale control

Slope, Louise N., Shah, Anokhi, Taylor, Michael J., Borghesani, Valentina, Caulton, Simon G., Brooks, Nikolas J., Hadley, Kate A., Rose, Georgina, Hunter, Robert I., Mkami, Hassane E. L., Smith, Graham M., Leney, Aneika C., Buurma, Niklaas J. ORCID: https://orcid.org/0000-0003-0260-5057, Lovering, Andrew L., Lovett, Janet E. and Peacock, Anna F. A. 2026. Design of a site selective heterochromic bimetallic lanthanide coiled coil with nanometre-scale control. Chemical Science 17 (25) , pp. 12313-12323. 10.1039/d6sc00813e

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Abstract

Lanthanide-protein scaffolds hold significant promise for the design of functional biomaterials. Yet the selective incorporation of multiple lanthanide ions with distinct properties into discrete sites at tuneable distances within a single construct remains a key challenge. Here, we report the rational design and structural characterization of the first de novo coiled coil capable of binding two different lanthanide ions at independent, non-equivalent sites with defined intermetallic spacing. By installing orthogonal coordination environments, comprising Asn3Asp3 and Asp3-only motifs, at defined positions along the coiled coil axis, we achieve precise, site-specific metal binding across a series of constructs spanning 1 to 5 nm. Site occupancy and intermetallic distances were validated using luminescence, electron paramagnetic resonance (EPR) spectroscopy, mass spectrometry and X-ray crystallography. The latter reveals the first structure of a coiled coil bound to two Tb3+ ions, and the shortest non-bridged metal–metal distance reported to date in such a scaffold (11.9 Å). The chemically distinct coordination sites enable sequential and selective metal loading. Remarkably, this system is capable of binding two different lanthanides, Tb3+ and Yb3+, at distinct sites, despite their extremely similar coordination chemistries. These results establish a robust and modular platform for constructing nanometre-scale molecular rulers, and highlight new avenues for the rational design of multifunctional metalloproteins.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Chemistry
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/3.0/, Start Date: 2026-05-12
Publisher:	Royal Society of Chemistry
ISSN:	2041-6520
Date of First Compliant Deposit:	27 May 2026
Date of Acceptance:	12 May 2026
Last Modified:	05 Aug 2026 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/187239

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