N-Terminal Protein Binding and Disorder-to-Order Transition by a Synthetic Receptor

Authors

• Niamh M. Mockler, University of Galway
• Kiefer O. Ramberg, University of Galway
• Ronan J. Flood, University of Galway
• Peter B. Crowley, University of Galway

ORCID

• Kiefer O. Ramberg: 0000-0002-3991-4809

Abstract

We describe the capture and structuring of disordered N-terminal regions by the macrocycle sulfonato-calix[4]arene (sclx₄). Using the trimeric β-propeller Ralstonia solanacearum lectin (RSL) as a scaffold, we generated a series of mutants with extended and dynamic N-termini. Three of the mutants feature an N-terminal methionine-lysine motif. The fourth mutant contains the disordered 8-residue N-terminus of Histone 3, a component of the nucleosome. X-ray crystallography and NMR spectroscopy provide evidence for sclx₄ binding to the flexible N-terminal regions. Three crystal structures reveal that the calixarene recognizes the N-terminal Met-Lys motif, capturing either residue. We provide crystallographic proof for sclx₄ encapsulation of N-terminal methionine. Calixarene capture of intrinsically disordered regions may have applications in regulating protein secondary (and tertiary) structure.

DOI Link

10.1021/acs.biochem.4c00729

Publication Date

2025-03-04

Publication Title

Biochemistry

Volume

64

Issue

5

ISSN

0006-2960

First Page

1092

Last Page

1098

Deposit Date

2026-05-01

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Additional Links

https://www.scopus.com/pages/publications/85218272223

Recommended Citation

Mockler, Niamh M.; Ramberg, Kiefer O.; Flood, Ronan J.; and Crowley, Peter B., "N-Terminal Protein Binding and Disorder-to-Order Transition by a Synthetic Receptor" (2025). Research Outputs: 2025-Present. 34.
https://arrow.tudublin.ie/scschcpsro/34