9gr5

Publication Abstract from PubMed

We describe the capture and structuring of disordered N-terminal regions by the macrocycle sulfonato-calix[4]arene (sclx(4)). Using the trimeric beta-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.

N-Terminal Protein Binding and Disorder-to-Order Transition by a Synthetic Receptor.,Mockler NM, Ramberg KO, Flood RJ, Crowley PB Biochemistry. 2025 Mar 4;64(5):1092-1098. doi: 10.1021/acs.biochem.4c00729. Epub , 2025 Feb 20. PMID:39977527^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.