Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Mechanisms of Protein Oligomerization, the Critical Role of Insertions and Deletions in Maintaining Different Oligomeric States
Many proteins form homooligomeric complexes in a cell. Proteins that exist in different oligomeric states are responsible for the diversity and specificity of many pathways, and transitions between different oligomeric states may regulate protein activity. Despite the importance of homooligomers, the mechanisms of oligomerization are not very well understood and general principles have not been formulated. In our study, we analyze sequence and structural features of homologous proteins in different oligomeric states, and how they are involved in the interface formation (1). We show that insertions and deletions which differentiate monomers and dimers have a significant tendency to be located on the interaction interfaces. We also show that about a quarter of all proteins and forty percent of enzymes in our dataset have regions which mediate or disrupt the formation of homooligomers. These results suggest that relatively small insertions or deletions may have a profound effect on complex stability. Indeed, in many cases removal of enabling regions caused the strong destabilization of the complexes. Moreover, we find that enabling regions contain a larger fraction of hydrophilic residues, glycine and proline compared to conventional interfaces and surfaces, resulting in a lower aggregation propensity. Most likely, these regions may mediate specific interactions, prevent non-specific dysfunctional aggregation and preclude undesired interactions between close paralogs therefore separating their functional pathways. When we closely examine the glycosyltransferase family, which consists of highly diverged members adopting different oligomeric states, we find that homooligomeric glycosyltransferases appear as ancient as monomeric ones and go back in evolution to the last universal common ancestor and many of them have enabling or disabling features on their interfaces (2).
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