Combinatorial protein engineering provides powerful means for functional selection of novel binding proteins. One class of engineered binding proteins, denoted affibodies, is based on the three-helix scaffold of the Z domain derived from staphylococcal protein A. The ZSPA-1 affibody has been selected from a phage-displayed library as a binder to protein A. ZSPA-1 also binds with micromolar affinity to its own ancestor, the Z domain. We have characterized the ZSPA-1 affibody in its uncomplexed state and determined the solution structure of a Z:ZSPA-1 protein–protein complex. Uncomplexed ZSPA-1 behaves as an aggregation-prone molten globule, but folding occurs on binding, and the original (Z) three-helix bundle scaffold is fully formed in the complex. The structural basis for selection and strong binding is a large interaction interface with tight steric and polar/nonpolar complementarity that directly involves 10 of 13 mutated amino acid residues on ZSPA-1. We also note similarities in how the surface of the Z domain responds by induced fit to binding of ZSPA-1 and Ig Fc, respectively, suggesting that the ZSPA-1 affibody is capable of mimicking the morphology of the natural binding partner for the Z domain.