Theresa Frank

Suche


A6 Functional selectivity as a result of viral chemokine receptor heterodimerization

Principal investigator
Nuska Tschammer

Mentor
Thomas Stamminger

Functional selectivity as a result of viral chemokine receptor heteromerization

Chemokines and their G protein-coupled receptors (GPCRs) are key players in the immune defense by directing and controlling the recruitment of leukocytes to lymphoid tissues and sites of inflammation. Certain herpesviruses, including human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), are known to encode viral G protein-coupled receptors (vGPCRs) that often show high similarity to human chemokine receptors. The reprogramming of cell signaling by vGPCRs is often aimed at facilitating dissemination of the virus, preventing immune surveillance and establishing life-long latency.
As the involvement of viral GPCRs in immune-evasion and herpesvirus-associated inflammatory as well as proliferative diseases cannot be neglected, there is high interest in developing agents targeting these receptors. To this point the project aims to identify novel compounds that could serve as potential antivirals. The main focus of the project is the role of the HCMV encoded vGPCRs with special interest in their propensity to form heterodimers with host chemokine receptors. The influence of heterodimerization on the ligand binding and signaling of these receptors will be dissected in detail. A combination of protein complementation and bioluminescence resonance energy transfer assays will be used to exclusively detect signaling originating from heterodimeric receptor complexes.

Figure: Functional selectivity after heteromerization of the viral GPCR US28 with host chemokine receptors. Heterodimerization of different GPCRs can change the functional characteristics of the individual partners, which include trafficking, ligand binding and signaling. This phenomenon is known as functional selectivity or biased signaling.

 

Publications

 

Presentations

October 2016 8th Annual Retreat, Erlangen School of Molecular Communication, Schloss Schney, Lichtenfels, Germany
”The HCMV encoded G protein-coupled US28 receptor abates surface expression and signaling of the human chemokine receptor CXCR4”
Poster
     
February 2016 G Protein-Coupled Receptors, Structure, Signaling and Drug Discovery, Keystone, Colorado, USA
”The HCMV encoded G protein-coupled US28 receptor abates surface expression and signaling of  human chemokine receptor CXCR4”
Poster
     
October 2015 2nd International SFB 796 Conference: Mechanisms of microbial host cell manipulation: From plants to humans, Erlangen, Germany
The HCMV encoded G protein-coupled US28 receptor abates surface expression and signaling of human chemokine receptors CXCR3 and CXCR4
Poster
     
July 2015

7th Annual Retreat, Erlangen School of Molecular Communication, Schloss Hirschberg, Beilngries, Germany
”Probing viral chemokine receptor heteromerization and their functional consequences using BRET and luciferase complementation”

Talk
     
September 2013

7th Summerschool “Medicinal Chemistry”, Regensburg, Germany
“Monitoring heterodimerization of viral G-protein coupled receptor US28 with human chemokine receptors”

Poster
     

 

Awards

Best Poster Award

Second place

8th Annual Retreat, Erlangen School of Molecular Communication, Schloss Schney, Lichtenfels, Germany, October 2016
“The HCMV encoded G protein-coupled US28 receptor abates surface expression and signaling of the human chemokine receptor CXCR4“

Best Talk Award

Third place

7th Annual Retreat, Erlangen School of Molecular Communication, Schloss Hirschberg, Beilngries, Germany, July 2015
“Probing viral chemokine receptor heteromerization and their functional consequences using BRET and luciferase complementation“