A novel strategy for designing and synthesizing extremely thermostable biologically active proteins is proposed. The design concept is based on combining a rigid and extremely hydrophobic peptide unit with a biologically active peptide unit. The cell adhesive peptide sequence, Arg-Gly-Asp (RGD), as a functional peptide unit was incorporated into the elastin-based rigid polyhexapeptide, whose repeating unit is Ala-Pro-Gly-Val-Gly-Val (APGVGV). The designed fusion gene was expressed in E. coli, and the resulting protein, designated ER4, was purified with affinity chromatography. The ER4-coated cell culture plate showed sufficient cell adhesive activity through the RGD sequence on the surface of ER4. The thermostability of ER4 was demonstrated by estimating the remaining cell adhesive activity after autoclaving at 120 degreesC for 20 min, and it retained over 90% of cell adhesive activity compared with native ER4.