Computer-Assisted Identification of Protein Sorting Signals and Prediction of Membrane Protein Topology and Structure

Many proteins contain sorting signals that serve to target them for import into different subcellular compartments. Similar signals also guide the insertion of integral membrane proteins into lipid bilayers. This chapter describes current methods for detecting such signals in amino acid sequences. Many of the functional characteristics of proteins can be correlated with more or less well-defined linear motifs in their amino acid sequences. This chapter deals with motifs that are known to be important for intracellular protein sorting, i.e., with sequence elements that serve as “address labels” and allow the cell to transport a given class of proteins to a given subcellular organelle. As it turns out, related motifs also guide membrane proteins into the lipid bilayer. In most cases, these motifs are encoded within a simple, contiguous stretch of the chain, and are thus, quite easy to identify in the primary sequence. The understanding of the signals that guide the assembly of membrane proteins is sufficiently advanced to allow quite reliable predictions of topology from sequence, at least for bacterial inner membrane proteins.