An albumin-derived peptide scaffold capable of binding and catalysis

PLoS One. 2013;8(2):e56469. doi: 10.1371/journal.pone.0056469. Epub 2013 Feb 22.

Abstract

We have identified a 101-amino-acid polypeptide derived from the sequence of the IIA binding site of human albumin. The polypeptide contains residues that make contact with IIA ligands in the parent protein, and eight cysteine residues to form disulfide bridges, that stabilize the polypeptide structure. Seventy-four amino acids are located in six α-helical regions, while the remaining thirty-seven amino acids form six connecting coil/loop regions. A soluble GST fusion protein was expressed in E. coli in yields as high as 4 mg/l. This protein retains the IIA fragment's capacity to bind typical ligands such as warfarin and efavirenz and other albumin's functional properties such as aldolase activity and the ability to direct the stereochemical outcome of a diketone reduction. This newly cloned polypeptide thus represents a valuable starting point for the construction of libraries of binders and catalysts with improved proficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins
  • Catalysis
  • Glutathione Transferase / chemistry
  • Humans
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Protein Binding
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism*
  • Serum Albumin / chemistry*

Substances

  • Albumins
  • Peptides
  • Recombinant Fusion Proteins
  • Serum Albumin
  • Glutathione Transferase

Grants and funding

Commissariato del Governo nella Regione Friuli – Venezia Giulia (Fondo Trieste Grant 597/08 “Piccoli peptidi per lo sviluppo di biosensori”) has funded this research project and has granted Immacolata Luisi, Silvia Pavan and Giampaolo Fontanive. Regione Piemonte “Piattaforma ImmOnc” has funded Daniele Sblattero. The funders (Commissariato del Governo nella regione Friuli - Venezia Giulia, fondo Trieste, grant 597/08; Regione Piemonte, piattaforma ImmunOc) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.