Hand-in-hand work of physics and evolution delivered protein universe with diversity of forms, sizes, and functions. Pervasiveness and advantageous traits of allostery made it an important component of the protein function regulation, calling for thorough investigation of its structural determinants and evolution. Learning directly from nature, we explored here allosteric communication in several major folds and repeat proteins, including α/β and β-barrels, β-propellers, Ig-like fold, ankyrin and α/β leucine-rich repeat proteins, which provide structural platforms for many different enzymatic and signalling functions. We obtained a picture of conserved allosteric communication characteristic in different fold types, modifications of the structure-driven signalling patterns via sequence-determined divergence to specific functions, as well as emergence and potential diversification of allosteric regulation in multi-domain proteins and oligomeric assemblies. Our observations will be instrumental in facilitating the engineering and de novo design of proteins with allosterically regulated functions, including development of therapeutic biologics. In particular, results described here may guide the identification of the optimal structural platforms (e.g. fold type, size, and oligomerization states) and the types of diversifications/perturbations, such as mutations, effector binding, and order–disorder transition. The tunable allosteric linkage across distant regions can be used as a pivotal component in the design/engineering of modular biological systems beyond the traditional scaffolding function.