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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.

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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.

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Examples of Quaternary Structure Topologies(A) All QSTs for complexes with up to nine subunits are shown, accounting for more than 96% of the nonredundant set of QSs and more than 98% of all complexes in PDB. Topologies compatible with a symmetrical complex are annotated with an s, and topologies where all subunits have the same number of interfaces (edges) are annotated by a star (*).(B) Examples of large complexes that are the single representatives of their respective topologies (QSTs). PDB codes are given. 1pf9, E. coli GroEL-GroES-ADP; 1eaf, synthetic construct, pyruvate dehydrogenase; 1shs, Methanococcus jannaschii small heat shock protein; 1b5s, Bacillus stearothermophilus dihydrolipoyl transacetylase; 1j2q, Archaeoglobus fulgidus 20S protesome alpha ring. It is interesting to note that the graph layouts resemble the spatial arrangements of the subunits.(C) Likely errors in the PDB Biological Units: QSTs of homomers with different numbers of contacts amongst the subunits. The number of erroneous QSs in each topology is provided above each graph.
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pcbi-0020155-g003: Examples of Quaternary Structure Topologies(A) All QSTs for complexes with up to nine subunits are shown, accounting for more than 96% of the nonredundant set of QSs and more than 98% of all complexes in PDB. Topologies compatible with a symmetrical complex are annotated with an s, and topologies where all subunits have the same number of interfaces (edges) are annotated by a star (*).(B) Examples of large complexes that are the single representatives of their respective topologies (QSTs). PDB codes are given. 1pf9, E. coli GroEL-GroES-ADP; 1eaf, synthetic construct, pyruvate dehydrogenase; 1shs, Methanococcus jannaschii small heat shock protein; 1b5s, Bacillus stearothermophilus dihydrolipoyl transacetylase; 1j2q, Archaeoglobus fulgidus 20S protesome alpha ring. It is interesting to note that the graph layouts resemble the spatial arrangements of the subunits.(C) Likely errors in the PDB Biological Units: QSTs of homomers with different numbers of contacts amongst the subunits. The number of erroneous QSs in each topology is provided above each graph.

Mentions: QS topologies represent the number of subunits (nodes) in a complex and the pattern of interfaces (edges) between them, and is thus a topological level only. In mathematical terms, a QS topology is an unlabelled connected graph. The number of possible graphs for a given number of nodes N can be calculated and increases dramatically with N [25]. A single QS topology exists for N = 1 or N = 2, while there are 6 QS topologies for N = 4, and 261,080 for N = 9. Comparatively, we observe a low number, 192 QS topologies in total, that account for the 21,037 protein complexes. This low number suggests that some QS topologies are preferred over others in the protein universe. All the QS topologies containing up to nine chains are shown in Figure 3, and the number above each QST indicates the number of QSs (nonredundant structures) it corresponds to. A visual inspection of the QSTs suggests three main constraints limiting their number.


3D complex: a structural classification of protein complexes.

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

Examples of Quaternary Structure Topologies(A) All QSTs for complexes with up to nine subunits are shown, accounting for more than 96% of the nonredundant set of QSs and more than 98% of all complexes in PDB. Topologies compatible with a symmetrical complex are annotated with an s, and topologies where all subunits have the same number of interfaces (edges) are annotated by a star (*).(B) Examples of large complexes that are the single representatives of their respective topologies (QSTs). PDB codes are given. 1pf9, E. coli GroEL-GroES-ADP; 1eaf, synthetic construct, pyruvate dehydrogenase; 1shs, Methanococcus jannaschii small heat shock protein; 1b5s, Bacillus stearothermophilus dihydrolipoyl transacetylase; 1j2q, Archaeoglobus fulgidus 20S protesome alpha ring. It is interesting to note that the graph layouts resemble the spatial arrangements of the subunits.(C) Likely errors in the PDB Biological Units: QSTs of homomers with different numbers of contacts amongst the subunits. The number of erroneous QSs in each topology is provided above each graph.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-0020155-g003: Examples of Quaternary Structure Topologies(A) All QSTs for complexes with up to nine subunits are shown, accounting for more than 96% of the nonredundant set of QSs and more than 98% of all complexes in PDB. Topologies compatible with a symmetrical complex are annotated with an s, and topologies where all subunits have the same number of interfaces (edges) are annotated by a star (*).(B) Examples of large complexes that are the single representatives of their respective topologies (QSTs). PDB codes are given. 1pf9, E. coli GroEL-GroES-ADP; 1eaf, synthetic construct, pyruvate dehydrogenase; 1shs, Methanococcus jannaschii small heat shock protein; 1b5s, Bacillus stearothermophilus dihydrolipoyl transacetylase; 1j2q, Archaeoglobus fulgidus 20S protesome alpha ring. It is interesting to note that the graph layouts resemble the spatial arrangements of the subunits.(C) Likely errors in the PDB Biological Units: QSTs of homomers with different numbers of contacts amongst the subunits. The number of erroneous QSs in each topology is provided above each graph.
Mentions: QS topologies represent the number of subunits (nodes) in a complex and the pattern of interfaces (edges) between them, and is thus a topological level only. In mathematical terms, a QS topology is an unlabelled connected graph. The number of possible graphs for a given number of nodes N can be calculated and increases dramatically with N [25]. A single QS topology exists for N = 1 or N = 2, while there are 6 QS topologies for N = 4, and 261,080 for N = 9. Comparatively, we observe a low number, 192 QS topologies in total, that account for the 21,037 protein complexes. This low number suggests that some QS topologies are preferred over others in the protein universe. All the QS topologies containing up to nine chains are shown in Figure 3, and the number above each QST indicates the number of QSs (nonredundant structures) it corresponds to. A visual inspection of the QSTs suggests three main constraints limiting their number.

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
Related in: MedlinePlus