Limits...
3D complex: a structural classification of protein complexes.

Levy ED, Pereira-Leal JB, Chothia C, Teichmann SA - PLoS Comput. Biol. (2006)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom. elevy@mrc-lmb.cam.ac.uk

ABSTRACT
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.

Show MeSH
The Size of Homomeric Complexes in the Protein Data Bank and in SwissProtThe histogram shows the relative abundances of monomers and homo-oligomers of different sizes in the PDB and in SwissProt. Two PDB sets are shown: the complete set and the nonredundant set of QSs. Three SwissProt sets are shown: the complete SwissProt and the Human and E. coli subsets. The trend in all the sets is similar and highlights the importance of the mechanism of self-assembly, which is linked to many functional possibilities discussed in the text. The oligomeric state of proteins in SwissProt was extracted from the subunit annotation field, and annotations inferred by similarity were not considered.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1636673&req=5

pcbi-0020155-g007: The Size of Homomeric Complexes in the Protein Data Bank and in SwissProtThe histogram shows the relative abundances of monomers and homo-oligomers of different sizes in the PDB and in SwissProt. Two PDB sets are shown: the complete set and the nonredundant set of QSs. Three SwissProt sets are shown: the complete SwissProt and the Human and E. coli subsets. The trend in all the sets is similar and highlights the importance of the mechanism of self-assembly, which is linked to many functional possibilities discussed in the text. The oligomeric state of proteins in SwissProt was extracted from the subunit annotation field, and annotations inferred by similarity were not considered.

Mentions: Interestingly, the trend in the PDB is in close agreement with our observations in SwissProt as shown in Figure 7. In the PDB, we observe 46% of homo-oligomers in the complete set, 60% in the nonredundant set, and between 71% and 73% in SwissProt. Thus, our nonredundant set is more similar to SwissProt than the entire PDB. There is agreement at an even more detailed level in all five datasets: even numbers of subunits are favoured among complexes of size four or more. Homomers with an odd number of subunits can only adopt cyclic symmetries, while even-numbered homomers with four or more subunits can adopt either dihedral or cyclic symmetries [41] (Figure 6). Therefore, the preference for even numbers of subunits suggests that most of these complexes adopt a dihedral symmetry. Indeed, PDB complexes of size four or more with an even number of subunits adopt dihedral symmetries in 80% of the cases and cyclic in 20%. Presumably this is because evolution and stability of dihedral complexes is more favourable than for cyclic complexes. The close agreement between the PDB and SwissProt supports the PDB as a representative set of QSTs.


3D complex: a structural classification of protein complexes.

Levy ED, Pereira-Leal JB, Chothia C, Teichmann SA - PLoS Comput. Biol. (2006)

The Size of Homomeric Complexes in the Protein Data Bank and in SwissProtThe histogram shows the relative abundances of monomers and homo-oligomers of different sizes in the PDB and in SwissProt. Two PDB sets are shown: the complete set and the nonredundant set of QSs. Three SwissProt sets are shown: the complete SwissProt and the Human and E. coli subsets. The trend in all the sets is similar and highlights the importance of the mechanism of self-assembly, which is linked to many functional possibilities discussed in the text. The oligomeric state of proteins in SwissProt was extracted from the subunit annotation field, and annotations inferred by similarity were not considered.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1636673&req=5

pcbi-0020155-g007: The Size of Homomeric Complexes in the Protein Data Bank and in SwissProtThe histogram shows the relative abundances of monomers and homo-oligomers of different sizes in the PDB and in SwissProt. Two PDB sets are shown: the complete set and the nonredundant set of QSs. Three SwissProt sets are shown: the complete SwissProt and the Human and E. coli subsets. The trend in all the sets is similar and highlights the importance of the mechanism of self-assembly, which is linked to many functional possibilities discussed in the text. The oligomeric state of proteins in SwissProt was extracted from the subunit annotation field, and annotations inferred by similarity were not considered.
Mentions: Interestingly, the trend in the PDB is in close agreement with our observations in SwissProt as shown in Figure 7. In the PDB, we observe 46% of homo-oligomers in the complete set, 60% in the nonredundant set, and between 71% and 73% in SwissProt. Thus, our nonredundant set is more similar to SwissProt than the entire PDB. There is agreement at an even more detailed level in all five datasets: even numbers of subunits are favoured among complexes of size four or more. Homomers with an odd number of subunits can only adopt cyclic symmetries, while even-numbered homomers with four or more subunits can adopt either dihedral or cyclic symmetries [41] (Figure 6). Therefore, the preference for even numbers of subunits suggests that most of these complexes adopt a dihedral symmetry. Indeed, PDB complexes of size four or more with an even number of subunits adopt dihedral symmetries in 80% of the cases and cyclic in 20%. Presumably this is because evolution and stability of dihedral complexes is more favourable than for cyclic complexes. The close agreement between the PDB and SwissProt supports the PDB as a representative set of QSTs.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom. elevy@mrc-lmb.cam.ac.uk

ABSTRACT
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.

Show MeSH