A buildup approach to the design of a small-sized protein via an autonomously-folded short segment

• Project/Area Number: 22760617
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biofunction/Bioprocess
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: WATANABE Hideki 独立行政法人産業技術総合研究所, バイオメディカル研究部門, 研究員 (90422089)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 生物機能工学 / 人工蛋白質 / 分子進化工学 / 抗体医薬 / ファージディスプレイ

Research Abstract

This study established a methodology for the design of small-sized proteins on the basis of segment elongation by using chignolin that was introduced as a structural support. Using T7 phage displayed library, we selected artificial proteins with affinity for antibody Fc region that was used as a model target. Function and three dimensional structures of artificial proteins were analyzed in detail by using surface plasmon resonance, NMR, and X-ray crystallography.

Research Products

• [Journal Article] Tracing primordial protein evolution through structurally guided stepwise segment elongation (2014)
  • Author(s): Hideki Watanabe, Kazuhiko Yamasaki, Shinya Honda
  • Journal Title: J. Biol. Chem Volume: vol. 289 Issue: 6 Pages: 3394-3404
  • DOI: 10.1074/jbc.m113.530592
  • Peer Reviewed / Open Access
• [Journal Article] Structure-based histidine substitution for optimizing pH-sensitive Staphylococcus protein A (2013)
  • Author(s): Hideki Watanabe, Hiroyuki Matsumaru, Ayako Ooishi, Shinya Honda
  • Journal Title: J. Chromatogr. B Volume: vol. 929 Pages: 155-160
  • DOI: 10.1016/j.jchromb.2013.04.029
  • Peer Reviewed
• [Journal Article] Biomimetic engineering of modular bispecific antibodies for biomolecule immobilization (2011)
  • Author(s): Hideki Watanabe
  • Journal Title: Langmuir Volume: 27 Issue: 16 Pages: 9656-966
  • DOI: 10.1021/la2006259
  • Peer Reviewed
• [Journal Article] ～抗体医療研究の技術を工業材料開発へ～ 抗体分子の「ナノ糊(のり)としての利用 (2011)
  • Author(s): 渡邊秀樹, 梅津光央, 熊谷泉
  • Journal Title: Material Stage Volume: vol. 10 Pages: 6-9
• [Journal Article] ～抗体医療研究の技術を工業材料開発へ～抗体分子の「ナノ糊(のり)としての利用」 (2011)
  • Author(s): 渡邊秀樹、梅津光央、熊谷泉
  • Journal Title: MATERIAL STAGE Volume: 10-10 Pages: 6-9
• [Journal Article] 分子デザインによる抗体精製用蛋白質プロテインGの安定性およびpH応答性の論理的改変 (2010)
  • Author(s): 渡邊秀樹, 本田真也
  • Journal Title: BIO INDUSTRY Volume: vol. 27 Pages: 72-78
• [Journal Article] 分子デザインによる抗体精製用蛋白質プロテインGの安定性およびpH応答性の論理的改変 (2010)
  • Author(s): 渡邊秀樹、本田真也
  • Journal Title: BIO INDUSTRY Volume: 27-12 Pages: 72-78
• [Patent(Industrial Property Rights)] 抗体結合性ペプチド (2013)
  • Inventor(s): 渡邊秀樹, 本田真也
  • Industrial Property Rights Holder: 独立行政法人産業技術総合研究所
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-12-25
  • Overseas
• [Patent(Industrial Property Rights)] 微小タンパク質の骨格構造に基づく分子ライブラリ (2013)
  • Inventor(s): 本田真也, 渡邊秀樹, 山崎和彦
  • Industrial Property Rights Holder: 独立行政法人産業技術総合研究所
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-12-09
  • Overseas