4-2 Protein Profiling

Some sequence-comparison methods also try to include secondary and tertiary structural information. Because different secondary structural elements can be formed from very similar segments of sequence (see section 4-14), using structural information in the description of the reference protein could, in theory at least, help exclude proteins with somewhat similar sequences but very different structures. It is also known that even similar proteins can have shifts in the relative positions of sequence segments, dictated by differences in secondary-structure packing and the positioning of functionally important groups. This makes the similarity at the sequence level very difficult to determine. For example, there are prokaryotic SH3 domains which, like their eukaryotic relatives, bind to proline-rich sequences. Straightforward sequence alignment does not indicate any relationship between the prokaryotic and eukaryotic domains; however, when the alignment is performed by comparing residues in the corresponding secondary structure elements of the prokaryotic and eukaryotic domains, some regions of sequence conservation appear. A number of small functional domains that can be characterized in this way are listed in Figure 4-6.