Adaptation of protein surfaces to subcellular location

TitleAdaptation of protein surfaces to subcellular location
Publication TypeJournal Article
Year of Publication1998
AuthorsAndrade, MA, O'Donoghue, SI, Rost, B
JournalJ Mol Biol
KeywordsAmino Acids/analysis/chemistry Cell Nucleus/chemistry/*metabolism Cytoplasm/chemistry/*metabolism Extracellular Matrix/chemistry/metabolism Glycosylation *Models, Biological Models, Molecular Protein Conformation Proteins/*chemistry/*metabolism

In vivo, proteins occur in widely different physio-chemical environments, 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. In this paper, we have approached this problem by grouping proteins by their subcellular location and looking at structural properties that are characteristic to each location. We hypothesize that, throughout evolution, each subcellular location has maintained a characteristic physio-chemical environment, and that proteins in each location have adapted to these environments. If so, we would expect that protein structures from different locations will show characteristic differences, particularly at the surface, which is directly exposed to the environment. To test this hypothesis, we have examined all eukaryotic proteins with known three-dimensional structure and for which the subcellular location is known to be either nuclear, cytoplasmic, or extracellular. In agreement with previous studies, we find that the total amino acid composition carries a signal that identifies the subcellular location. This signal was due almost entirely to the surface residues. The surface residue signal was often strong enough to accurately predict subcellular location, given only a knowledge of which residues are at the protein surface. The results suggest how the accuracy of prediction of location from sequence can be improved. We concluded that protein surfaces show adaptation to their subcellular location. The nature of these adaptations suggests several principles that proteins may have used in adapting to particular physio-chemical environments; these principles may be useful for protein design.