Location-dependent lanthanide selectivity engineered into structurally characterized designed coiled coils

Louise N Slope; Oliver J Daubney; Hannah Campbell; Scott A White; Anna F A Peacock

doi:10.1002/anie.202110500

Location-dependent lanthanide selectivity engineered into structurally characterized designed coiled coils

Louise N Slope, Oliver J Daubney, Hannah Campbell, Scott A White, Anna F A Peacock

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Abstract

Herein we report unprecedented location-dependent, size-selective binding to designed lanthanide (Ln³⁺ ) sites within miniature protein coiled coil scaffolds. Not only do these engineered sites display unusual Ln³⁺ selectivity for moderately large Ln³⁺ ions (Nd to Tb), for the first time we demonstrate that selectivity can be location-dependent and can be programmed into the sequence. A 1 nm linear translation of the binding site towards the N-terminus can convert a selective site into a highly promiscuous one. An X-ray crystal structure, the first of a lanthanide binding site within a coiled coil to be reported, coupled with CD studies, reveal the existence of an optimal radius that likely stems from the structural constraints of the coiled coil scaffold. To the best of our knowledge this is the first report of location-dependent metal selectivity within a coiled coil scaffold, as well as the first report of location-dependent Ln³⁺ selectivity within a protein.

Original language	English
Pages (from-to)	24473-24477
Number of pages	5
Journal	Angewandte Chemie (International Edition)
Volume	60
Issue number	46
Early online date	8 Sept 2021
DOIs	https://doi.org/10.1002/anie.202110500
Publication status	Published - 8 Nov 2021

Bibliographical note

Funding Information:
We thank the School of Chemistry, the EPSRC (EP/L504907/1) and the University of Birmingham for a Ph.D. studentship for L.N.S., and the Defence Science and Technology Laboratory (Dstl) for a Ph.D. studentship for O.J.D., the Centre for Chemical and Materials Analysis in the School of Chemistry. We thank Diamond Light Source for access to beamline ID04-1 (MX14 692) that contributed to the results presented here, and finally we thank Dr John Wilkie for stimulating discussions.

Publisher Copyright:
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH

Keywords

bioinorganic chemistry
coiled coils
lanthanides
peptides
protein design

ASJC Scopus subject areas

Catalysis
Chemistry(all)

Access to Document

10.1002/anie.202110500Licence: Creative Commons: Attribution (CC BY)

SlopeLN2021LocationFinal published version, 1.33 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

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title = "Location-dependent lanthanide selectivity engineered into structurally characterized designed coiled coils",

abstract = "Herein we report unprecedented location-dependent, size-selective binding to designed lanthanide (Ln3+ ) sites within miniature protein coiled coil scaffolds. Not only do these engineered sites display unusual Ln3+ selectivity for moderately large Ln3+ ions (Nd to Tb), for the first time we demonstrate that selectivity can be location-dependent and can be programmed into the sequence. A 1 nm linear translation of the binding site towards the N-terminus can convert a selective site into a highly promiscuous one. An X-ray crystal structure, the first of a lanthanide binding site within a coiled coil to be reported, coupled with CD studies, reveal the existence of an optimal radius that likely stems from the structural constraints of the coiled coil scaffold. To the best of our knowledge this is the first report of location-dependent metal selectivity within a coiled coil scaffold, as well as the first report of location-dependent Ln3+ selectivity within a protein.",

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note = "Funding Information: We thank the School of Chemistry, the EPSRC (EP/L504907/1) and the University of Birmingham for a Ph.D. studentship for L.N.S., and the Defence Science and Technology Laboratory (Dstl) for a Ph.D. studentship for O.J.D., the Centre for Chemical and Materials Analysis in the School of Chemistry. We thank Diamond Light Source for access to beamline ID04-1 (MX14 692) that contributed to the results presented here, and finally we thank Dr John Wilkie for stimulating discussions. Publisher Copyright: {\textcopyright} 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH",

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N2 - Herein we report unprecedented location-dependent, size-selective binding to designed lanthanide (Ln3+ ) sites within miniature protein coiled coil scaffolds. Not only do these engineered sites display unusual Ln3+ selectivity for moderately large Ln3+ ions (Nd to Tb), for the first time we demonstrate that selectivity can be location-dependent and can be programmed into the sequence. A 1 nm linear translation of the binding site towards the N-terminus can convert a selective site into a highly promiscuous one. An X-ray crystal structure, the first of a lanthanide binding site within a coiled coil to be reported, coupled with CD studies, reveal the existence of an optimal radius that likely stems from the structural constraints of the coiled coil scaffold. To the best of our knowledge this is the first report of location-dependent metal selectivity within a coiled coil scaffold, as well as the first report of location-dependent Ln3+ selectivity within a protein.

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Location-dependent lanthanide selectivity engineered into structurally characterized designed coiled coils

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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