3D Complex: A Structural Classification of Protein Complexes

Most of the proteins in a cell assemble into complexes to carry out their function. It is therefore crucial to understand the physicochemical properties as well as the evolution of interactions between proteins. The Protein Data Bank represents an important source of information for such studies, because more than half of the structures are homo- or heteromeric protein complexes. Here we propose the first hierarchical classification of whole protein complexes of known 3-D structure, based on representing their fundamental structural features as a graph. This classification provides the first overview of all the complexes in the Protein Data Bank and allows nonredundant sets to be derived at different levels of detail. This reveals that between one-half and two-thirds of known structures are multimeric, depending on the level of redundancy accepted. We also analyse the structures in terms of the topological arrangement of their subunits and find that they form a small number of arrangements compared with all theoretically possible ones. This is because most complexes contain four subunits or less, and the large majority are homomeric. In addition, there is a strong tendency for symmetry in complexes, even for heteromeric complexes. Finally, through comparison of Biological Units in the Protein Data Bank with the Protein Quaternary Structure database, we identified many possible errors in quaternary structure assignments. Our classification, available as a database and Web server at http://www.3Dcomplex.org, will be a starting point for future work aimed at understanding the structure and evolution of protein complexes. The millions of genes sequenced over the past decade correspond to a much smaller set of protein structural domains, or folds—probably only a few thousand. Since structural data is being accumulated at a fast pace, classifications of domains such as SCOP help significantly in understanding the sequence–structure relationship. More recently, classifications of interacting domain pairs address the relationship between sequence divergence and domain–domain interaction. One level of description that has yet to be investigated is the protein complex level, which is the physiologically relevant state for most proteins within the cell. Here, Levy and colleagues propose a classification scheme for protein complexes, which will allow a better understanding of their structural properties and evolution.