Are protein–protein interfaces more conserved in sequence than the rest of the protein surface?

Caffrey, Daniel R.; Somaroo, Shyamal; Hughes, Jason D.; Mintseris, Julian; Huang, Enoch S.

doi:10.1110/ps.03323604

Cited by 324 publications

(270 citation statements)

References 75 publications

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“…Sensitive conservation analyses have been proposed to detect functional sites within proteins (18)(19)(20) and have further been used for the identification of protein-binding sites (21)(22)(23)(24)(25)(26). However, conservation does not provide mutual information between interacting partners so as to identify the residue pairs in contact.…”

mentioning

confidence: 99%

Coevolution at protein complex interfaces can be detected by the complementarity trace with important impact for predictive docking

Madaoui

Guérois

2008

Proc. Natl. Acad. Sci. U.S.A.

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Protein surfaces are under significant selection pressure to maintain interactions with their partners throughout evolution. Capturing how selection pressure acts at the interfaces of proteinprotein complexes is a fundamental issue with high interest for the structural prediction of macromolecular assemblies. We tackled this issue under the assumption that, throughout evolution, mutations should minimally disrupt the physicochemical compatibility between specific clusters of interacting residues. This constraint drove the development of the so-called Surface COmplementarity Trace in Complex History score (SCOTCH), which was found to discriminate with high efficiency the structure of biological complexes. SCOTCH performances were assessed not only with respect to other evolution-based approaches, such as conservation and coevolution analyses, but also with respect to statistically based scoring methods. Validated on a set of 129 complexes of known structure exhibiting both permanent and transient intermolecular interactions, SCOTCH appears as a robust strategy to guide the prediction of protein-protein complex structures. Of particular interest, it also provides a basic framework to efficiently track how protein surfaces could evolve while keeping their partners in contact.evolution ͉ prediction ͉ protein-protein interaction T he modular assembly of proteins is a key determinant in the regulation of biological systems. Combinations of inter-and intramolecular interactions hold the cell machineries and govern the flow of information transmitted through cell signaling pathways. To unravel the complexity of cell organization, atlases of the physical interactome have been obtained for several model organisms (1, 2). To further elucidate the competitions and synergies ruling the molecular logic of these protein-protein interaction networks, a critical step relies on the structural characterization of the protein complexes. However, there is still a huge gap between the proteome-wide data accumulating and the available structural details of macromolecular complexes.A number of studies have tackled the large-scale analysis of protein-protein complexes from a structural perspective (3-7). They have emphasized that size, shape, and the physicochemical complementarities at the interfaces are key descriptors that could be used to develop computational methods able to predict protein-binding sites from sequences or structures (8)(9)(10)(11)(12)(13)(14). In the context of evolution, seminal studies compared the binding modes of domain-domain interactions between homologous proteins and concluded that they tend to interact similarly, even if sequence identity has been maintained as low as 30% (15, 16). Such a low conservation threshold suggests that interaction surfaces can evolve significantly while maintaining sufficient specificity between the binding partners. The paradox between sequence divergence and structural conservation of macromolecular assemblies has been recently related to the notion of superfamily, and the exis...

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mentioning

confidence: 99%

Coevolution at protein complex interfaces can be detected by the complementarity trace with important impact for predictive docking

Madaoui

Guérois

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…These suggestions are based on the idea that most domains and domain interactions are evolutionary conserved, and consequently, proteins will interact if they contain domains that are known to associate [12,3]. Thus, the suggestion of novel protein interactions is performed by looking at all domains of a protein, using the Pfam database.…”

Section: Novel Protein Interactionsmentioning

confidence: 99%

“…A protein-protein interaction is established by protein domains, which are encoded in protein sequences and form individual and independent structures. These domains and the resulting protein interactions are highly regulated and evolutionary conserved [12,3]. One major topic of systems biology is the investigation and identification of known and predicted protein-protein interactions to reveal new cellular pathways, disturbed cell processes or even create complete interactomes of organisms [1,5].…”

Section: Introductionmentioning

confidence: 99%

ProDGe: investigating protein-protein interactions at the domain level

Büchel¹,

Wrzodek²,

Mittag³

et al. 2011

Nature Precedings

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An important goal of systems biology is the identification and investigation of known and predicted proteinprotein interactions to obtain more information about new cellular pathways and processes. Proteins interact via domains, thus it is important to know which domains a protein contains and which domains interact with each other. Here we present the Java TM program ProDGe (Protein Domain Gene), which visualizes existing and suggests novel domain-domain interactions and protein-protein interactions at the domain level. The comprehensive dataset behind ProDGe consists of protein, domain and interaction information for both layers, collected and combined appropriately from UniProt, Pfam, DOMINE and IntAct. Based on known domain interactions, ProDGe suggests novel protein interactions and assigns them to four confidence classes, depending on the reliability of the underlying domain interaction. Furthermore, ProDGe is able to identify potential homologous interaction partners in other species, which is particularly helpful when investigating poorly annotated species. We further evaluated and compared experimentally identified protein interactions from IntAct with domain interactions from DOMINE for six species and noticed that 31.13% of all IntAct protein interactions in all six species can be mapped to the actual interacting domains. ProDGe and a comprehensive documentation are freely available at

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“…The role of the remaining residues not contributing to the binding affinity is thought largely to be to exclude solvent (Bogan and Thorn, 1998). These residues are less constrained evolutionarily and do not affect specificity (Caffrey et al, 2004;Guharoy and Chakrabarti, 2005). Even among the binding interface residues that contribute to the binding affinity, the degree of amino acid sensitivity between similar amino acids is unclear.…”

Section: Mutational Opportunities After Duplicate Gene Birthmentioning

confidence: 99%

Understanding Gene Duplication Through Biochemistry and Population Genetics

Liberles

Kolesov

Dittmar

2010

Evolution After Gene Duplication

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Gene duplication has emerged as an important process supporting the functional diversification of genes. Since publication of the seminal book Evolution by Gene Duplication by Ohno (1970), the hypothesis regarding the importance of gene duplication in the generation of evolutionary novelty has steadily gained support as we have entered the genome-sequencing era. It is through the link to functional biology that an ultimate understanding of the preservation and diversification of duplicate genes will be accomplished.Genes can diverge in function through accumulation (fixation) of coding sequence changes, which may influence binding interactions and/or catalysis, through the evolution of splice variants, and through spatial, temporal, and concentration-level changes in the expression of the protein product. Governing these processes is an interplay among mutational opportunity, population dynamics, protein biochemistry, and systems and organismal biology. This interplay is described systematically in this chapter. SYSTEMS BIOLOGY AND HIGHER-LEVEL ORGANIZATIONAt the level of biological systems, two early but still relevant views suggested a role for gene duplication in constructing pathways. These views are both dependent on a new function emerging in one of the duplicates, but differ in the manner in which it occurs. One view, patchwork evolution, involved a conservation of catalytic activity coupled with the evolution of a new substrate after duplication (Jensen, 1976). An alternative view, retrograde evolution, suggested that pathways are built up backward, with product becoming substrate based on recognition of the transition state in the Evolution After Gene Duplication, Edited by Katharina Dittmar and David Liberles

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Are protein–protein interfaces more conserved in sequence than the rest of the protein surface?

Cited by 324 publications

References 75 publications

Coevolution at protein complex interfaces can be detected by the complementarity trace with important impact for predictive docking

Coevolution at protein complex interfaces can be detected by the complementarity trace with important impact for predictive docking

ProDGe: investigating protein-protein interactions at the domain level

Understanding Gene Duplication Through Biochemistry and Population Genetics

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