Hertle, Regina and Nazet, Julian and Semmelmann, Florian and Schlee, Sandra and Funke, Franziska and Merkl, Rainer and Sterner, Reinhard (2021) Reprogramming the Specificity of a Protein Interface by Computational and Data-Driven Design. STRUCTURE, 29 (3). 292-+. ISSN 0969-2126, 1878-4186
Full text not available from this repository. (Request a copy)Abstract
The formation of specific protein complexes in a cell is a non-trivial problem given the co-existence of thousands of different polypeptide chains. A particularly difficult case are two glutamine amidotransferase complexes (anthranilate synthase [AS] and aminodeoxychorismate synthase [ADCS]), which are composed of homologous pairs of synthase and glutaminase subunits. We have attempted to identify discriminating interface residues of the glutaminase subunit TrpG from AS, which are responsible for its specific interaction with the synthase subunit TrpEx and prevent binding to the closely related synthase subunit PabB from ADCS. For this purpose, TrpG-specific interface residues were grafted into the glutaminase subunit PabA from ADCS by two different approaches, namely a computational and a data-driven one. Both approaches resulted in PabA variants that bound TrpEx with higher affinity than PabB. Hence, we have accomplished a reprogramming of protein-protein interaction specificity that provides insights into the evolutionary adaptation of protein interfaces.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EVOLUTION; DYNAMICS; CONSERVATION; ANTIBODIES; CHORISMATE; SYNTHASE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Reinhard Sterner Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Rainer Merkl |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Jul 2022 09:11 |
| Last Modified: | 06 Jul 2022 09:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45670 |
Actions (login required)
 |
View Item |
