Evolutionary diversification of protein–protein interactions by interface add-ons
| Autor: | Markus Busch, Leonhard Heizinger, Florian Busch, Rainer Merkl, Maximilian G. Plach, Florian Semmelmann, Vicki H. Wysocki, Reinhard Sterner |
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| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular 0301 basic medicine Multidisciplinary 030102 biochemistry & molecular biology Protein Conformation Interface (Java) Archaeal Proteins In silico Protein design In vivo analysis Computational biology Biology Biological Evolution Protein–protein interaction 03 medical and health sciences 030104 developmental biology PNAS Plus Bacterial Proteins Biochemistry Protein Interaction Domains and Motifs Protein–protein interaction prediction Databases Protein Function (biology) Protein Binding Glutamine amidotransferase |
| Zdroj: | Proceedings of the National Academy of Sciences. 114 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1707335114 |
| Popis: | Cells contain a multitude of protein complexes whose subunits interact with high specificity. However, the number of different protein folds and interface geometries found in nature is limited. This raises the question of how protein-protein interaction specificity is achieved on the structural level and how the formation of nonphysiological complexes is avoided. Here, we describe structural elements called interface add-ons that fulfill this function and elucidate their role for the diversification of protein-protein interactions during evolution. We identified interface add-ons in 10% of a representative set of bacterial, heteromeric protein complexes. The importance of interface add-ons for protein-protein interaction specificity is demonstrated by an exemplary experimental characterization of over 30 cognate and hybrid glutamine amidotransferase complexes in combination with comprehensive genetic profiling and protein design. Moreover, growth experiments showed that the lack of interface add-ons can lead to physiologically harmful cross-talk between essential biosynthetic pathways. In sum, our complementary in silico, in vitro, and in vivo analysis argues that interface add-ons are a practical and widespread evolutionary strategy to prevent the formation of nonphysiological complexes by specializing protein-protein interactions. |
| Databáze: | OpenAIRE |
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