Review Article | Published:

Large-scale functional analysis using peptide or protein arrays

Nature Biotechnology volume 18, pages 393397 (2000) | Download Citation

Subjects

Abstract

The array format for analyzing peptide and protein function offers an attractive experimental alternative to traditional library screens. Powerful new approaches have recently been described, ranging from synthetic peptide arrays to whole proteins expressed in living cells. Comprehensive sets of purified peptides and proteins permit high-throughput screening for discrete biochemical properties, whereas formats involving living cells facilitate large-scale genetic screening for novel biological activities. In the past year, three major genome-scale studies using yeast as a model organism have investigated different aspects of protein function, including biochemical activities, gene disruption phenotypes, and protein–protein interactions. Such studies show that protein arrays can be used to examine in parallel the functions of thousands of proteins previously known only by their DNA sequence.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & DNA microarrays in drug discovery and development. Nat. Genet. 21(1 Suppl), 48–50 (1999).

  2. 2.

    , & DNA chips: promising toys have become powerful tools. Trends Biochem. Sci. 24, 168–173 (1999).

  3. 3.

    & Molecular linguistics: extracting information from gene and protein sequences. Proc. Natl. Acad. Sci. USA. 94, 5506–5507 (1997).

  4. 4.

    et al. Light-generated oligonucleotide arrays for rapid DNA sequence analysis. Proc. Natl. Acad. Sci. USA 91, 5022–5026 (1994).

  5. 5.

    & 2D protein electrophoresis: can it be perfected? Curr. Opin. Biotechnol. 10, 16–21 (1999).

  6. 6.

    & Proteomics and automation. Electrophoresis 20, 664–677 (1999).

  7. 7.

    , & Electrospray ionization and matrix assisted laser desorption/ionization mass spectrometry: powerful analytical tools in recombinant protein chemistry. Nat. Biotechnol. 14, 449–457 (1996).

  8. 8.

    et al. Predicting function: from genes to genomes and back. J. Mol. Biol. 283, 707–725 (1998).

  9. 9.

    , , , & A combined algorithm for genome-wide prediction of protein function. Nature 402, 83–86 (1999).

  10. 10.

    et al. A new type of synthetic peptide library for identifying ligand-binding activity. Nature 354, 82–84 (1991).

  11. 11.

    et al. Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery. Nature 354, 84–86 (1991).

  12. 12.

    , & Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc. Natl. Acad. Sci. USA 81, 3998–4002 (1984).

  13. 13.

    et al. Systematic screening for bioactive peptides. Pept. Res. 4, 142–146 (1991).

  14. 14.

    , , & Automated multiple peptide synthesis. Pept. Res. 5, 315–320 (1992).

  15. 15.

    & Synthesis and screening of peptide libraries on continuous cellulose membrane supports. Methods Mol. Biol. 87, 25–39 (1998).

  16. 16.

    , , , & Simultaneous synthesis of peptide libraries on single resin and continuous cellulose membrane supports: examples for the identification of protein, metal and DNA binding peptide mixtures. Pept. Res. 6, 314–319 (1993).

  17. 17.

    et al. Mapping protein-protein contact sites using cellulose-bound peptide scans. Mol. Divers. 1, 141–148 (1996).

  18. 18.

    et al. Regions of endonuclease EcoRII involved in DNA target recognition identified by membrane-bound peptide repertoires. J. Biol. Chem. 274, 5213–5221 (1999).

  19. 19.

    et al. A synthetic mimic of a discontinuous binding site on interleukin-10. Nat. Biotechnol. 17, 271–275 (1999).

  20. 20.

    et al. Amino acid specificity of glycation and protein-AGE crosslinking reactivities determined with a dipeptide SPOT library. Nat. Biotechnol. 17, 1006–1010 (1999).

  21. 21.

    et al. Light-directed, spatially addressable parallel chemical synthesis. Science 251, 767–773 (1991).

  22. 22.

    , , & Peptides on phage: a vast library of peptides for identifying ligands. Proc. Natl. Acad. Sci. USA. 87, 6378–6382 (1990).

  23. 23.

    , , , & Improved performances of spot multiple peptide synthesis. Pept. Res. 9, 151–155 (1996).

  24. 24.

    & Immunoassay and other ligand assays: present status and future trends. J. Int. Fed. Clin. Chem. 9, 100–109 (1997).

  25. 25.

    et al. Array biosensor for simultaneous identification of bacterial, viral, and protein analytes. Anal. Chem. 71, 3846–3852 (1999).

  26. 26.

    , , , & Mass-sensing, multianalyte microarray immunoassay with imaging detection. Clin. Chem. 44, 2036–2043 (1998).

  27. 27.

    & New desorption strategies for the mass spectrometric analysis of macromolecules. Rapid Commun. Mass Spectrom. 7, 576–580 (1993).

  28. 28.

    , , , & The role of cholesterol in the biosynthesis of beta-amyloid. Neuroreport 10, 1699–1705 (1999).

  29. 29.

    , , , & Micropatterned immobilization of a G protein-coupled receptor and direct detection of G protein activation. Nat. Biotechnol. 17, 1105–1108 (1999).

  30. 30.

    et al. A biochemical genomics approach for identifying genes by the activity of their products. Science 286, 1153–1155 (1999).

  31. 31.

    , , & Recombination-mediated PCR-directed plasmid construction in vivo in yeast. Nucleic Acids Res. 25, 451–452 (1997).

  32. 32.

    , , & A new logic for DNA engineering using recombination in Escherichia coli. Nat. Genet. 20, 123–128 (1998).

  33. 33.

    et al. Genome-scale cloning and expression of individual open reading frames using topoisomerase I-mediated ligation. Genome Res. 9, 383–392 (1999).

  34. 34.

    , , , & Affinity fusion strategies for detection, purification, and immobilization of recombinant proteins. Protein Expr. Purif. 11, 1–16 (1997).

  35. 35.

    et al. A generic protein purification method for protein complex characterization and proteome exploration. Nat. Biotechnol. 17, 1030–1032 (1999).

  36. 36.

    et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627 (2000).

  37. 37.

    et al. Life with 6000 genes. Science 274, 546, 563–567 (1996).

  38. 38.

    & Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast. Nature 364, 121–126 (1993).

  39. 39.

    , & Identification of RNAs that bind to a specific protein using the yeast three-hybrid system. RNA 5, 596–601 (1999).

  40. 40.

    , , & Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins. Proc. Natl. Acad. Sci. USA 93, 4604–4607 (1996).

  41. 41.

    & A three-hybrid system for detecting small ligand-protein receptor interactions. Proc. Natl. Acad. Sci. USA 93, 12817–12821 (1996).

  42. 42.

    et al. Large-scale analysis of the yeast genome by transposon tagging and gene disruption. Nature 402, 413–418 (1999).

  43. 43.

    , & An in vitro polysome display system for identifying ligands from very large peptide libraries. Proc. Natl. Acad. Sci. USA 91, 9022–9026 (1994).

  44. 44.

    & RNA-peptide fusions for the in vitro selection of peptides and proteins. Proc. Natl. Acad. Sci. USA 94, 12297–12302 (1997).

  45. 45.

    , , & Changing functionality of surfaces by directed self-assembly using oligonucleotides–the oligo-tag. Biotechniques 27, 752–760 (1999).

  46. 46.

    et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906 (1999).

  47. 47.

    Genetics: a touch of elegance with RNAi. Curr. Biol. 9, R440–R442 (1999).

  48. 48.

    & Using GFP in FRET-based applications. Trends Cell Biol. 9, 57–60 (1999).

  49. 49.

    & Imaging biomolecule arrays by atomic force microscopy. Biophys. J. 68, 1653–1660 (1995).

  50. 50.

    Macromolecular matchmaking: advances in two-hybrid and related technologies. Curr. Opin. Biotechnol. 9, 90–96 (1998).

Download references

Acknowledgements

We thank Michael DeVit, Andrew Emili, Stanley Fields, Stephen McCraith, Eric Phizicky, Chandra Tucker, and Peter Uetz for comments on the manuscript, and Deborah Diamond for helpful suggestions. This work was supported by NIH grants GM54415 and RR11823 and a grant from the Merck Genome Research Institute. A.Q.E. is a research associate of the Howard Hughes Medical Institute.

Author information

Affiliations

  1. Departments of Genetics and Medicine, University of Washington, Seattle, WA 98195

    • Alia Qureshi Emili
    •  & Gerard Cagney
  2. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195

    • Alia Qureshi Emili

Authors

  1. Search for Alia Qureshi Emili in:

  2. Search for Gerard Cagney in:

Corresponding author

Correspondence to Gerard Cagney.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/74442

Further reading