Aromatic interactions in homeodomains contribute to the low quantum yield of a conserved, buried tryptophan

Vikas Nanda, Ludwig Brand

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Trp 48, a conserved, buried residue commonly found in the hydrophobic core of homeodomains, has an unusually low fluorescence quantum yield. Chemical denaturation of Drosophila homeodomains Engrailed and Antennapedia(C39S) result in a four-fold increase in quantum yield, while unfolding of Ultrabithorax causes a twenty-fold enhancement. Global analysis of time-resolved fluorescence decay monitored at multiple emission wavelengths reveals sub-nanosecond lifetime components which dominate the overall intensity. Based on structure and sequence analysis of several homeodomains, we deduce that quenching is due to a transient, excited-state Nit ... π hydrogen bond involving Trp 48 and a conserved aromatic residue at position 8. Additionally, both time-resolved fluorescence of indole-benzene mixtures and an electrostatic model of the proposed tryptophan-aromatic interaction substantiate different aspects of this mechanism. A survey of the Protein Data Bank reveals many proteins with tryptophanaromatic pairs where the indole nitrogen participates in a NH...π hydrogen bond with the ring of another aromatic residue. Chemical denaturation of one protein found in this survey, human fibronectin type III module 10, causes an enhancement of the fluorescence quantum yield. This unique interaction has implications for many other systems and may be useful for studying larger, multi-tryptophan containing proteins. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)112-125
Number of pages14
JournalProteins: Structure, Function and Genetics
Volume40
Issue number1
DOIs
StatePublished - Jul 1 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Keywords

  • Fibronectin type III
  • Fluorescence
  • NH ... π hydrogen bond
  • Protein unfolding
  • Quenching

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