Plach, Maximilian G. and Semmelmann, Florian and Busch, Florian and Busch, Markus and Heizinger, Leonhard and Wysocki, Vicki H. and Merkl, Rainer and Sterner, Reinhard (2017) Evolutionary diversification of protein-protein interactions by interface add-ons. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114 (40). E8333-E8342. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
Cells contain amultitude 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BACILLUS-SUBTILIS; TRYPTOPHAN BIOSYNTHESIS; INTERACTION SPECIFICITY; ANTHRANILATE SYNTHASE; FOLIC-ACID; DOMAIN; SIGNAL; GENE; AMIDOTRANSFERASE; ARCHAEBACTERIA; protein-protein interactions; protein interfaces; interface add-on; glutamine amidotransferases; protein evolution |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 01 Mar 2019 08:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2026 |
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