The present invention is directed to compositions and methods including peptides which have a high affinity for each other and, when linked to a protein, are used to help fold the protein into a compact structure. By virtue of its stability and constraints, this scaffold can prolong the activity of any embedded protein sequences in the presence of cellular and other proteases. The compact structure can have other functional sequences embedded, and is preferable to linear and less constrained peptides for library screening, for creating structurally-biased peptide libraries and for targeting to specific intracellular and extracellular compartments. Compositions of the present invention can be displayed on the surface of viruses, archaebacteria, prokaryotic and eukaryotic cells for library screening, drug screening and display. Methods of the present invention are useful for screening in vivo for intracellular effector proteins modulating signaling pathways and to identify interacting proteins in vitro. Thus, the present invention is useful as a scaffold for gene therapy, for the isolation of new therapeutic drug leads and for potential use as a therapeutic in physiological fluids.