Calixarene-mediated assembly of a small antifungal protein

Jimi M. Alex, Martin L. Rennie, Sylvain Engilberge, Gábor Lehoczki, Hajdu Dorottya, Ádám Fizil, G. Batta, Peter B. Crowley

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Synthetic macrocycles such as calixarenes and cucurbiturils are increasingly applied as mediators of protein assembly and crystallization. The macrocycle can facilitate assembly by providing a surface on which two or more proteins bind simultaneously. This work explores the capacity of the sulfonato-calix[n]arene (sclx n ) series to effect crystallization of PAF, a small, cationic antifungal protein. Co-crystallization with sclx4, sclx6 or sclx8 led to high-resolution crystal structures. In the absence of sclx n , diffraction-quality crystals of PAF were not obtained. Interestingly, all three sclx n were bound to a similar patch on PAF. The largest and most flexible variant, sclx8, yielded a dimer of PAF. Complex formation was evident in solution via NMR and ITC experiments, showing more pronounced effects with increasing macrocycle size. In agreement with the crystal structure, the ITC data suggested that sclx8 acts as a bidentate ligand. The contributions of calixarene size/conformation to protein recognition and assembly are discussed. Finally, it is suggested that the conserved binding site for anionic calixarenes implicates this region of PAF in membrane binding, which is a prerequisite for antifungal activity.

Original languageEnglish
Pages (from-to)238-247
Number of pages10
JournalIUCrJ
Volume6
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Calixarenes
Crystallization
assembly
proteins
Proteins
crystallization
Protein Conformation
Crystal structure
crystal structure
Binding sites
Binding Sites
Dimers
Ligands
Conformations
Membranes
Diffraction
dimers
Nuclear magnetic resonance
membranes
nuclear magnetic resonance

Keywords

  • antifungal proteins
  • calixarene
  • conformation selection
  • molecular glue
  • nucleating agent
  • polyethylene glycol
  • supramolecular chemistry

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Materials Science(all)
  • Condensed Matter Physics

Cite this

Alex, J. M., Rennie, M. L., Engilberge, S., Lehoczki, G., Dorottya, H., Fizil, Á., ... Crowley, P. B. (2019). Calixarene-mediated assembly of a small antifungal protein. IUCrJ, 6, 238-247. https://doi.org/10.1107/S2052252519000411

Calixarene-mediated assembly of a small antifungal protein. / Alex, Jimi M.; Rennie, Martin L.; Engilberge, Sylvain; Lehoczki, Gábor; Dorottya, Hajdu; Fizil, Ádám; Batta, G.; Crowley, Peter B.

In: IUCrJ, Vol. 6, 01.01.2019, p. 238-247.

Research output: Contribution to journalArticle

Alex, JM, Rennie, ML, Engilberge, S, Lehoczki, G, Dorottya, H, Fizil, Á, Batta, G & Crowley, PB 2019, 'Calixarene-mediated assembly of a small antifungal protein', IUCrJ, vol. 6, pp. 238-247. https://doi.org/10.1107/S2052252519000411
Alex JM, Rennie ML, Engilberge S, Lehoczki G, Dorottya H, Fizil Á et al. Calixarene-mediated assembly of a small antifungal protein. IUCrJ. 2019 Jan 1;6:238-247. https://doi.org/10.1107/S2052252519000411
Alex, Jimi M. ; Rennie, Martin L. ; Engilberge, Sylvain ; Lehoczki, Gábor ; Dorottya, Hajdu ; Fizil, Ádám ; Batta, G. ; Crowley, Peter B. / Calixarene-mediated assembly of a small antifungal protein. In: IUCrJ. 2019 ; Vol. 6. pp. 238-247.
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