Work

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

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide We describe the capture and structuring of disordered N-terminal regions by the macrocycle sulfonato-calix[4]arene ( sclx 4 ). 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 sclx 4 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 sclx 4 encapsulation of N-terminal methionine. Calixarene capture of intrinsically disordered regions may have applications in regulating protein secondary (and tertiary) structure.

Source: Biochemistry

DOI: 10.1021/acs.biochem.4c00729

Authors: Niamh M. Mockler, Kiefer O. Ramberg, Ronan J. Flood, Peter B. Crowley

Institution: Ollscoil na Gaillimhe – University of Galway

Language: English

Topic: Supramolecular Chemistry and Complexes

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: Science Foundation Ireland, University of Galway, Irish Research Council