PhD Scientific Days 2026

Poster Session 3.U - Molecular Medicine

Diversity of β-arrestin binding in GPCRs: the role of core and C-terminal interactions

Előadó neve

Dr. Kis, Katalin

Neptune code

YG6XR9

Előadó munkahelye

Department of Physiology

Előadó telefonszáma

+36307513269

Előadó e-mail címe

kis.katalin@semmelweis.hu

Az előadás címe

Diversity of β-arrestin binding in GPCRs: the role of core and C-terminal interactions

Szerző(k) neve és munkahelye

Katalin Kis¹

1: Department of Physiology

Bemutatás módja

Poszter

Szekció

Poster Session 3.U - Molecular Medicine

Language of the presentation

Hungarian

Preferred session

Molecular Medicine

Összefoglaló szövege

Introduction
β-arrestins are involved in termination of GPCR signalling (desensitization) and internalization. They bind to receptors in two main ways: via a core interaction to the transmembrane core of the receptor, and via a C-terminal interaction to the phosphorylated intracellular tail region. GPCRs are traditionally classified into class A and B based on the stability of β-arrestin binding. Class A receptors (e.g. β2AR, V1A, CB1) show transient binding, whereas class B receptors (e.g. AT1R, V2R) form stable complexes that internalize into endosomes. The binding preferences of β-arrestin1 and β-arrestin2 isoforms may differ, but the structural basis of this is not fully understood.
Aims
Our aim was to map in detail the β-arrestin binding of different GPCRs. We investigated the role of the core and C-terminal binding interfaces of β-arrestins in numerous GPCRs, as well as how these influence the binding of β-arrestin1 and β-arrestin2 isoforms in class A and B receptors.
Method
We examined activation differences of β-arrestin1/2 isoforms and binding-site mutants in numerous class A and B GPCRs. We performed BRET-based measurements and confocal microscopy in cells expressing wild-type and mutant β-arrestins. Two mutant β-arrestins were used: K2A, which impairs the C-terminal interaction, and ΔFLR, which impairs the core interaction.
Results
The individual mutations reduced β-arrestin activation in certain receptors as expected, but to varying degrees; however, in other cases the loss of one binding interface enhanced recruitment through the other pathway. In some receptors both interaction interfaces were required, and mutation of either binding interface abolished β-arrestin activation.
Conclusion
Our results suggest that GPCRs cannot be simply classified into class A and B based on β-arrestin binding. Even receptors classified into the same class show significant differences: the contribution of core and C-terminal interactions differs and may also interact with each other, even in an inhibitory manner. The different preferences of β-arrestin1 and β-arrestin2 further increase the complexity of the system, suggesting a multi-state binding model.
Funding
This work was supported by the Hungarian National Research, Development, and Innovation Fund (NKFI FK 138862, K 139231).

kis.katalin@semmelweis.hu
Semmelweis University
Supervisors: Gábor Turu, László Hunyady

University

Semmelweis University

Supervisor

Gábor Turu, László Hunyady

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

9143

Start

14:12

End

14:15