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 languageEnglish
Pages (from-to)24473-24477
Number of pages5
JournalAngewandte Chemie (International Edition)
Volume60
Issue number46
Early online date8 Sept 2021
DOIs
Publication statusPublished - 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)

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