The protein common interface database (ProtCID)--a comprehensive database of interactions of homologous proteins in multiple crystal forms

Abstract

The protein common interface database (ProtCID) is a database that contains clusters of similar homodimeric and heterodimeric interfaces observed in multiple crystal forms (CFs). Such interfaces, especially of homologous but non-identical proteins, have been associated with biologically relevant interactions. In ProtCID, protein chains in the protein data bank (PDB) are grouped based on their PFAM domain architectures. For a single PFAM architecture, all the dimers present in each CF are constructed and compared with those in other CFs that contain the same domain architecture. Interfaces occurring in two or more CFs comprise an interface cluster in the database. The same process is used to compare heterodimers of chains with different domain architectures. By examining interfaces that are shared by many homologous proteins in different CFs, we find that the PDB and the Protein Interfaces, Surfaces, and Assemblies (PISA) are not always consistent in their annotations of biological assemblies in a homologous family. Our data therefore provide an independent check on publicly available annotations of the structures of biological interactions for PDB entries. Common interfaces may also be useful in studies of protein evolution. Coordinates for all interfaces in a cluster are downloadable for further analysis. ProtCiD is available at http://dunbrack2.fccc.edu/protcid.

Architecture and Assembly of HIV Integrase Multimers in the Absence of DNA Substrates

“…That caveat aside, the results are most consistent with a cross-linked population comprising alternate reaching dimer configurations as well as some core-core dimer forms. With respect to the wild type reaching dimer architecture, the NTD-core cross-link between Glu-35 and Lys-160 is likely to represent a biologically relevant interface, as a careful analysis using PROTCID (21) reveals that a common interface with these residues in close proximity exists in all two-domain (NTD ϩ core) IN proteins that have been crystallized to date, including those of HIV-1, HIV-2, PFV, and maedi visna virus. The interface (supplemental Fig.…”

Mouse modeling and structural analysis of the p.G307S mutation in human cystathionine β-synthase (CBS) reveal effects on CBS activity but not stability

“…In both cases, the ψ dihedral of the first residue in each pair is altered as is the ϕ of the next residue. This is typical of backbone flips in protein structures (39). In the simulation of the mutant dimer, chain A has flipped during the equilibration phase from the conformation seen in the wildtype protein (G307: ϕ,ψ=85°,147°; Y308: ϕ,ψ=-153°,166°) to another conformation that is more consistent with conformations typically seen for serine residues (S307: ϕ,ψ=100°,20°; Y308: ϕ,ψ=-80°,150°).…”

“…There are a total of 9 PDB entries of human CBS (1JBQ, 1M54, 4COO, 4L0D, 4L27, 4L28, 4L3V, 4PCU, and 5MMS) and 3 PDB entries of Drosophila CBS (3PC2, 3PC3, and 3PC4). Each structure contains the common dimer found in this family of PLP-dependent enzymes (39). The dimers found in the human structures are shown in Fig.…”

Computational Methods for Prediction of Protein-Protein Interaction Sites

“…There have been also a number of studies published on the structure-based mapping of interaction sites, utilizing different schemes of hit weighting and homology recognition. (Albou et al, 2011;Oldfield, 2002;Park et al, 2001;Xu and Dunbrack, 2011) However, it remains to be seen how structure-based mapping methods can deal with situations when a protein undergoes a significant conformational change upon complex formation (e.g., in case of calmodulin), and a structure alignment is likely to fail to identify similarity between apo-and holo-forms. Most likely, the future methods will utilize a balanced combination of sequence-and structure-based homology in order to more accurately map interaction sites from the known physical interactions.…”

“…(Xu and Dunbrack, 2011) PDB defines biological units as separate models in the same PDB file. In addition, both PISA and PDB may rename chain labels starting from 'A' within each BU.…”