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Title: Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry

Abstract

Highlights: • The conformational dynamics of β-arrestin1 or β-arrestin2 were analyzed by HDX-MS. • β-Strands II through IV were more dynamic in β-arrestin2 than in β-arrestin1. • The middle loop was less dynamic in β-arrestin2 than in β-arrestin1. • Upon pre-activation by the R169E mutation, β-arrestins became more dynamic. • Pre-activation affected a wider region of β-arrestin1 compared to β-arrestin2. - Abstract: Arrestins have important roles in G protein-coupled receptor (GPCR) signaling including desensitization of GPCRs and G protein-independent signaling. There have been four arrestins identified: arrestin1, arrestin2 (e.g. β-arrestin1), arrestin3 (e.g. β-arrestin2), and arrestin4. β-Arrestin1 and β-arrestin2 are ubiquitously expressed and regulate a broad range of GPCRs, while arrestin1 and arrestin4 are expressed in the visual system. Although the functions of β-arrestin1 and β-arrestin2 widely overlap, β-arrestin2 has broader receptor selectivity, and a few studies have suggested that β-arrestin1 and β-arrestin2 have distinct cellular functions. Here, we compared the conformational dynamics of β-arrestin1 and β-arrestin2 by hydrogen/deuterium exchange mass spectrometry (HDX-MS). We also used the R169E mutant as a pre-activation model system. HDX-MS data revealed that β-strands II through IV were more dynamic in β-arrestin2 in the basal state, while the middle loop was more dynamic in β-arrestin1. Withmore » pre-activation, both β-arrestin1 and β-arrestin2 became more flexible, but broader regions of β-arrestin1 became flexible compared to β-arrestin2. The conformational differences between β-arrestin1 and β-arrestin2 in both the basal and pre-activated states might determine their different receptor selectivities and different cellular functions.« less

Authors:
;  [1];  [2];  [3];  [1]
  1. School of Pharmacy, Sungkyunkwan University, Suwon (Korea, Republic of)
  2. College of Pharmacy & Department of Molecular Science and Technology, Ajou University, Suwon (Korea, Republic of)
  3. College of Pharmacy, Chonnam National University, Gwang-Ju (Korea, Republic of)
Publication Date:
OSTI Identifier:
22458458
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 457; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; COMPARATIVE EVALUATIONS; DEUTERIUM; GTP-ASES; HYDROGEN; MASS SPECTROSCOPY; MUTATIONS; RECEPTORS; SIGNALS

Citation Formats

Yun, Youngjoo, Kim, Dong Kyun, Seo, Min-Duk, Kim, Kyeong-Man, and Chung, Ka Young, E-mail: kychung2@skku.edu. Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2014.12.079.
Yun, Youngjoo, Kim, Dong Kyun, Seo, Min-Duk, Kim, Kyeong-Man, & Chung, Ka Young, E-mail: kychung2@skku.edu. Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry. United States. doi:10.1016/J.BBRC.2014.12.079.
Yun, Youngjoo, Kim, Dong Kyun, Seo, Min-Duk, Kim, Kyeong-Man, and Chung, Ka Young, E-mail: kychung2@skku.edu. Fri . "Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry". United States. doi:10.1016/J.BBRC.2014.12.079.
@article{osti_22458458,
title = {Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry},
author = {Yun, Youngjoo and Kim, Dong Kyun and Seo, Min-Duk and Kim, Kyeong-Man and Chung, Ka Young, E-mail: kychung2@skku.edu},
abstractNote = {Highlights: • The conformational dynamics of β-arrestin1 or β-arrestin2 were analyzed by HDX-MS. • β-Strands II through IV were more dynamic in β-arrestin2 than in β-arrestin1. • The middle loop was less dynamic in β-arrestin2 than in β-arrestin1. • Upon pre-activation by the R169E mutation, β-arrestins became more dynamic. • Pre-activation affected a wider region of β-arrestin1 compared to β-arrestin2. - Abstract: Arrestins have important roles in G protein-coupled receptor (GPCR) signaling including desensitization of GPCRs and G protein-independent signaling. There have been four arrestins identified: arrestin1, arrestin2 (e.g. β-arrestin1), arrestin3 (e.g. β-arrestin2), and arrestin4. β-Arrestin1 and β-arrestin2 are ubiquitously expressed and regulate a broad range of GPCRs, while arrestin1 and arrestin4 are expressed in the visual system. Although the functions of β-arrestin1 and β-arrestin2 widely overlap, β-arrestin2 has broader receptor selectivity, and a few studies have suggested that β-arrestin1 and β-arrestin2 have distinct cellular functions. Here, we compared the conformational dynamics of β-arrestin1 and β-arrestin2 by hydrogen/deuterium exchange mass spectrometry (HDX-MS). We also used the R169E mutant as a pre-activation model system. HDX-MS data revealed that β-strands II through IV were more dynamic in β-arrestin2 in the basal state, while the middle loop was more dynamic in β-arrestin1. With pre-activation, both β-arrestin1 and β-arrestin2 became more flexible, but broader regions of β-arrestin1 became flexible compared to β-arrestin2. The conformational differences between β-arrestin1 and β-arrestin2 in both the basal and pre-activated states might determine their different receptor selectivities and different cellular functions.},
doi = {10.1016/J.BBRC.2014.12.079},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 457,
place = {United States},
year = {Fri Jan 30 00:00:00 EST 2015},
month = {Fri Jan 30 00:00:00 EST 2015}
}