Redesigning Protein Cavities as a Strategy for Increasing Affinity in Protein-Protein Interaction: Interferon-gamma Receptor 1 as a Model

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F15%3A00447258" target="_blank" >RIV/86652036:_____/15:00447258 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1155/2015/716945" target="_blank" >http://dx.doi.org/10.1155/2015/716945</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1155/2015/716945" target="_blank" >10.1155/2015/716945</a>

Result language
angličtina
Original language name
Redesigning Protein Cavities as a Strategy for Increasing Affinity in Protein-Protein Interaction: Interferon-gamma Receptor 1 as a Model
Original language description
Combining computational and experimental tools, we present a new strategy for designing high affinity variants of a binding protein. The affinity is increased by mutating residues not at the interface, but at positions lining internal cavities of one ofthe interacting molecules. Filling the cavities lowers flexibility of the binding protein, possibly reducing entropic penalty of binding. The approach was tested using the interferon-gamma receptor 1 (IFN gamma R1) complex with IFN gamma as a model. Mutations were selected from 52 amino acid positions lining the IFN gamma R1 internal cavities by using a protocol based on FoldX prediction of free energy changes. The final four mutations filling the IFN gamma R1 cavities and potentially improving the affinity to IFN gamma were expressed, purified, and refolded, and their affinity towards IFN gamma was measured by SPR. While individual cavity mutations yielded receptor constructs exhibiting only slight increase of affinity compared to WT,
Czech name
—
Czech description
—

Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
—

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Similar results(10)