title: Adaptive Assembly: Maximizing the Potential of a Given Functional Peptide with a Tailor-Made Protein Scaffold.
abstract: Protein engineering that exploits known functional peptides holds great promise for generating novel functional proteins. Here we propose a combinatorial approach, termed adaptive assembly, which provides a tailor-made protein scaffold for a given functional peptide. A combinatorial library was designed to create a tailor-made scaffold, which was generated from β hairpins derived from a 10-residue minimal protein "chignolin" and randomized amino acid sequences. We applied adaptive assembly to a peptide with low affinity for the Fc region of human immunoglobulin G, generating a 54-residue protein AF.p17 with a 40,600-fold enhanced affinity. The crystal structure of AF.p17 complexed with the Fc region revealed that the scaffold fixed the active conformation with a unique structure composed of a short α helix, β hairpins, and a loop-like structure. Adaptive assembly can take full advantage of known peptides as assets for generating novel functional proteins.
authors: Biomedical Research Institute, the National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Higashi, Tsukuba, Ibaraki 305-8566, Japan.
authors: Hideki
authors: H
authors: Watanabe
authors: Biomedical Research Institute, the National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Higashi, Tsukuba, Ibaraki 305-8566, Japan. Electronic address: s.honda@aist.go.jp.
authors: Shinya
authors: S
authors: Honda
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D015202:Protein Engineering / Q000379:methods*; D017433:Protein Structure, Secondary
chemical_list: D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; C506175:chignolin