Protein-protein interactions and selection: Generation of molecule-binding proteins on the basis of tertiary structural information

Mitsuo Umetsu, Takeshi Nakanishi, Ryutaro Asano, Takamitsu Hattori, Izumi Kumagai

Research output: Contribution to journalShort surveypeer-review

8 Citations (Scopus)

Abstract

Antibodies and their fragments are attractive binding proteins because their high binding strength is generated by several hypervariable loop regions, and because high-quality libraries can be prepared from the vast gene clusters expressed by mammalian lymphocytes. Recent explorations of new genome sequences and protein structures have revealed various small, nonantibody scaffold proteins. Accurate structural descriptions of protein-protein interactions based on X-ray and NMR analyses allow us to generate binding proteins by using grafting and library techniques. Here, we review approaches for generating binding proteins from small scaffold proteins on the basis of tertiary structural information. Identification of binding sites from visualized tertiary structures supports the transfer of function by peptide grafting. The local library approach is advantageous as a go-between technique for grafted foreign peptide sequences and small scaffold proteins. The identification of binding sites also supports the construction of efficient libraries with a low probability of denatured variants, and, in combination with the design for library diversity, opens the way to increasing library density and randomized sequence lengths without decreasing density. Detailed tertiary structural analyses of protein-protein complexes allow accurate description of epitope locations to enable the design of and screening for multispecific, high-affinity proteins recognizing multiple epitopes in target molecules.

Original languageEnglish
Pages (from-to)2006-2014
Number of pages9
JournalFEBS Journal
Volume277
Issue number9
DOIs
Publication statusPublished - 2010 May

Keywords

  • Library design
  • Peptide grafting
  • Protein structure
  • Scaffold protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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