An analysis of protein domain linkers: their classification and role in protein folding

Protein Eng. 2002 Nov;15(11):871-9. doi: 10.1093/protein/15.11.871.

Abstract

Recent advances in protein engineering have come from creating multi-functional chimeric proteins containing modules from various proteins. These modules are typically joined via an oligopeptide linker, the correct design of which is crucial for the desired function of the chimeric protein. Here we analyse the properties of naturally occurring inter-domain linkers with the aim to design linkers for domain fusion. Two main types of linker were identified; helical and non-helical. Helical linkers are thought to act as rigid spacers separating two domains. Non-helical linkers are rich in prolines, which also leads to structural rigidity and isolation of the linker from the attached domains. This means that both linker types are likely to act as a scaffold to prevent unfavourable interactions between folding domains. Based on these results we have constructed a linker database intended for the rational design of linkers for domain fusion, which can be accessed via the Internet at http://mathbio.nimr.mrc.ac.uk.

MeSH terms

  • Chi-Square Distribution
  • Hydrophobic and Hydrophilic Interactions
  • Protein Conformation
  • Protein Folding*
  • Protein Structure, Tertiary*
  • Sequence Analysis, Protein