The single nucleotide ß-arrestin2 variant, A248T, resembles dynamical properties of activated arrestin

Özge ŞENSOY

doi:https://doi.org/10.3906/kim-1910-46

Makale detayları

The single nucleotide ß-arrestin2 variant, A248T, resembles dynamical properties of activated arrestin

Yazarlar:

Özge ŞENSOY

Yayıncı:

TUBITAK

Ana Başlıklar:

Uygulamalı fizik

Dergi:

Turkish Journal of Chemistry 2020 Vol.44 Issue 2, pp.409-420

Belge Tipi:

Makale

Yayın Tarihi:

2/2020

Belge Dili:

İngilizce

Document ID (Org No.):

2000725439

Sıklık:

İki Aylık

eISSN:

1303-6130

pISSN:

1300-0527

DOI:

https://doi.org/10.3906/kim-1910-46

Özet:

 

ß-arrestins are responsible for termination of G protein-coupled receptor  GPCR -mediated signaling. Association of single nucleotide variants with onset of crucial diseases has made this protein family hot targets in the field of GPCR-mediated pharmacology. However, impact of these mutations on function of these variants has remained elusive. In this study, structural and dynamical properties of one of ß-arrestin2  arrestin 3  variants, A248T, which has been identified in some cancer tissue samples, were investigated via molecular dynamics simulations. The results showed that the variant underwent structural rearrangements which are seen in crystal structures of active arrestin. Specifically, the "short helix" unravels and the "gate loop" swings forward as seen in crystal structures of receptor-bound and GPCR phosphopeptide-bound arrestin. Moreover, the "finger loop" samples upward position in the variant. Importantly, these regions harbor crucial residues that are involved in receptor binding interfaces. Cumulatively, these local structural rearrangements help the variant adopt active-like domain angle without perturbing the "polar core". Considering that phosphorylationofthereceptorisrequiredforactivationofarrestin, A248Tmightserveasamodelsystemtounderstand phosphorylation-independent activation mechanism, thus enabling modulation of function of arrestin variants which are activated independent of receptor phosphorylation as seen in cancer.

Makale detayları

The single nucleotide ß-arrestin2 variant, A248T, resembles dynamical properties of activated arrestin

Yazarlar: Özge ŞENSOY

Yayıncı: TUBITAK

Ana Başlıklar: Uygulamalı fizik

Dergi: Turkish Journal of Chemistry 2020 Vol.44 Issue 2, pp.409-420

Belge Tipi: Makale

Yayın Tarihi: 2/2020

Belge Dili: İngilizce

Document ID (Org No.): 2000725439

Sıklık: İki Aylık

eISSN: 1303-6130

pISSN: 1300-0527

DOI: https://doi.org/10.3906/kim-1910-46

Sayı

Yazarlar:

Özge ŞENSOY

Yayıncı:

TUBITAK

Ana Başlıklar:

Uygulamalı fizik

Dergi:

Turkish Journal of Chemistry 2020 Vol.44 Issue 2, pp.409-420

Belge Tipi:

Makale

Yayın Tarihi:

2/2020

Belge Dili:

İngilizce

Document ID (Org No.):

2000725439

Sıklık:

İki Aylık

eISSN:

1303-6130

pISSN:

1300-0527

DOI:

https://doi.org/10.3906/kim-1910-46