FACS-optimized mutants of the green fluorescent protein (GFP)

Brendan P. Cormack, Raphael H. Valdivia, Stanley Falkow

Research output: Contribution to journalArticlepeer-review

2399 Scopus citations

Abstract

We have constructed a library in Escherichia coli of mutant gfp genes (encoding green fluorescent protein, GFP) expressed from a tightly regulated inducible promoter. We introduced random amino acid (aa) substitutions in the twenty aa flanking the chromophore Ser-Tyr-Gly sequence at aa 65-67. We then used fluorescence-activated cell sorting (FAGS) to select variants of GFP that fluoresce between 20-and 35-fold more intensely than wild type (wt), when excited at 488 nm. Sequence analysis reveals three classes of aa substitutions in GFP. All three classes of mutant proteins have highly shifted excitation maxima. In addition, when produced in E. coli, the folding of the mutant proteins is more efficient than folding of wt GFP. These two properties contribute to a greatly increased (100-fold) fluorescence intensity, making the mutants useful for a number of applications.

Original languageEnglish (US)
Pages (from-to)33-38
Number of pages6
JournalGene
Volume173
Issue number1
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • FITC
  • Fluorescence intensity
  • Fluorescence-activated cell sorter
  • GFP mutation

ASJC Scopus subject areas

  • Genetics

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