Cooperative DNA binding and assembly by a bZip peptide-amphiphile

Raymond S. Tu, Rachel Marullo, Roger Pynn, Ronit Bitton, Havazelet Bianco-Peled, Matthew V. Tirrell

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The bipartite basic zipper (bZip) GCN4 peptide, containing a leucine zipper and a basic binding region, is a well-studied transcription factor that can be rationally adapted to control dimerization or assembly. We have covalently appended alkyl tails to the C-terminus (leucine zipper terminus) of a bZip sequence, yielding mono- and dialkyl bZip peptide-amphiphiles that allowed us to investigate how molecular design can control the formation of secondary structure and self-assembled structure. We demonstrate that these peptide-amphiphiles exhibit four qualities that are representative of their modular construction. First, circular dichroism confirms that self-assembly of peptide-amphiphiles above the critical micelle concentration (CMC) results in an enhanced α-helical secondary structure as peptide head groups are confined to the assembled interface with high local concentrations. Second, the binding of the peptide-amphiphiles to DNA yields a further increase in secondary structure, where the helicity of the basic binding region is stabilized by forming native-like contacts, an "induced fit mechanism". Third, competitive fluorescence binding assays show peptide-amphiphiles bind cooperatively to DNA well below the CMC, where DNA templates monomeric binding and hydrophobic forces promote cooperativity, but the ability of the peptide to recognize a specific DNA sequence is not retained. And fourth, SANS results demonstrate the assembly of large lamellar aggregates as peptide-amphiphiles complex with DNA, supporting a structural hypothesis in which peptide-amphiphiles bind to the DNA in a native-like 'standing' orientation. These designed synthetic molecular architectures are capable of hierarchical assembly making them useful as functional building blocks that may be applied to a variety of systems, including gene delivery and artificial transcription factors.

Original languageEnglish
Pages (from-to)1035-1044
Number of pages10
JournalSoft Matter
Volume6
Issue number5
DOIs
StatePublished - 1 Mar 2010
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry (all)
  • Condensed Matter Physics

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