ADAPTATION OF PROTEIN SURFACES TO SUBCELLULAR LOCATION

In vivo, proteins occur in widely different physio-chemical environmen ts, and, from in vitro studies, we know that protein structure can be very sensitive to environment. However, theoretical studies of protein structure have tended to ignore this complexity. Ln this paper, we ha ve approached this problem by grouping proteins by their subcellular l ocation and looking at structural properties that are characteristic t o each location. We hypothesize that, throughout evolution, each subce llular location has maintained a characteristic physio-chemical enviro nment, and that proteins in each location have adapted to these enviro nments. If so, we would expect that protein structures from different locations will show characteristic differences, particularly at the su rface, which is directly exposed to the environment. To test this hypo thesis, we have examined all eukaryotic proteins with known three-dime nsional structure and for which the subcellular location is known to b e either nuclear, cytoplasmic, or extracellular. In agreement with pre vious studies, we find that the total am;no acid composition carries a signal that identifies the subcellular location. This signal was due almost entirely to the surface residues. The surface residue signal wa s often strong enough to accurately predict subcellular location, give n only a knowledge of which residues are at the protein surface. The r esults suggest how the accuracy of prediction of location from sequenc e can be improved. We concluded that protein surfaces show adaptation to their subcellular location. The nature of these adaptations suggest s several principles that proteins may have used in adapting to partic ular physio-chemical environments; these principles may be useful for protein design. (C) 1998 Academic Press Limited.