Molecular size scaling in families of protein native folds

The mean size of the most compact native states of globular proteins, independent of folding type, follows the scaling law of collapsed polymers R g ~ n 1/3 , relating the radius of gyration R g to the number of protein residues, n . Until now, this behaviour has only been observed within a small subset of unrelated single-domain proteins with n < 300. Here, we employ the SCOP database of protein folds to study systematically the scaling behaviour of well-defined families of domains that share structural and functional characteristics. In the particular case of helical proteins, we identify the folding types that can be associated with scaling laws corresponding to compact behaviour (e.g., the cytochrome- C monodomains) and noncompact behaviour (e.g., the immunoglobulin/albumin-binding and spectrin-repeat domains). Our results quantify the size variations within some folding families, as well as reveal that some distinct folds represent structures with equivalent compactness.