Evaluation of chemical cross-linkers for in-depth structural analysis of G protein-coupled receptors through cross-linking mass spectrometry.

Chromatography, Gel Chromatography, Liquid Cross-Linking Reagents / chemistry Glucagon-Like Peptide-1 Receptor / chemistry Ligands Molecular Dynamics Simulation Protein Conformation Protein Stability Receptors, Adrenergic, alpha-2 / chemistry Tandem Mass Spectrometry / methods
Cross-linking mass spectrometry GPCR Integral membrane protein chemical cross-linker structural dynamics

Journal

Analytica chimica acta
ISSN: 1873-4324
Titre abrégé: Anal Chim Acta
Pays: Netherlands
ID NLM: 0370534

Informations de publication

Date de publication:
15 Mar 2020
Historique:
received: 07 10 2019
revised: 12 12 2019
accepted: 15 12 2019
entrez: 12 2 2020
pubmed: 12 2 2020
medline: 26 11 2020
Statut: ppublish

Résumé

Chemical cross-linking would conceivably cause structural disruption of a protein, but few cross-linkers have been fully evaluated in this aspect. Furthermore, integral membrane proteins may differ from soluble proteins in the selection of suitable cross-linkers, which has never been investigated. In this study, we systematically evaluated the impact of five conventional cross-linkers targeting Lys, Asp and Glu, and two Arg-reactive cross-linkers on the structural and functional integrity of two G protein-coupled receptors (GPCRs). Perturbation of the receptor structure and ligand-binding activity was observed, depending on the receptor and cross-linking conditions. In particular, our study demonstrated that the concentrations of PDH and KArGO need to be fine-tuned in order to minimize the structural and functional disturbance of specific GPCRs. A set of amenable cross-linkers was selected to acquire the most comprehensive cross-link maps for two GPCRs. Our in-depth cross-linking mass spectrometry (CXMS) analysis has revealed dynamic features of structural regions in GPCRs that are not observable in the crystal structures. Thus, CXMS analysis of GPCRs using the expanded toolkit would facilitate structural modeling of uncharacterized receptors and gain new insights into receptor-ligand interactions.

Identifiants

DOI: 10.1016/j.aca.2019.12.036 PMID: 32043996
pubmed: 32043996
pii: S0003-2670(19)31492-8
doi: 10.1016/j.aca.2019.12.036
pii:
doi:

Substances chimiques

Cross-Linking Reagents 0
Glucagon-Like Peptide-1 Receptor 0
Ligands 0
Receptors, Adrenergic, alpha-2 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

53-62

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Lisha Xia (L)

iHuman Institute, ShanghaiTech University, 201210, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Ziliang Ma (Z)

iHuman Institute, ShanghaiTech University, 201210, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Jiahui Tong (J)

iHuman Institute, ShanghaiTech University, 201210, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.

Yuliang Tang (Y)

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, And Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 10087, China.

Shanshan Li (S)

iHuman Institute, ShanghaiTech University, 201210, Shanghai, China.

Shanshan Qin (S)

iHuman Institute, ShanghaiTech University, 201210, Shanghai, China.

Ronghui Lou (R)

iHuman Institute, ShanghaiTech University, 201210, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.

Suwen Zhao (S)

iHuman Institute, ShanghaiTech University, 201210, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.

Xiaoguang Lei (X)

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, And Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 10087, China. Electronic address: xglei@pku.edu.cn.

Wenqing Shui (W)

iHuman Institute, ShanghaiTech University, 201210, Shanghai, China; School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China. Electronic address: shuiwq@shanghaitech.edu.cn.

Articles similaires

Atomic view of photosynthetic metabolite permeability pathways and confinement in synthetic carboxysome shells.

Daipayan Sarkar, Christopher Maffeo, Markus Sutter et al.
1.00
Photosynthesis Ribulose-Bisphosphate Carboxylase Carbon Dioxide Molecular Dynamics Simulation Cyanobacteria

Drug repurposing against fucosyltransferase-2 via docking, STD-NMR, and molecular dynamic simulation studies.

Muhammad Atif, Humaira Zafar, Atia-Tul- Wahab et al.
1.00
Fucosyltransferases Drug Repositioning Molecular Docking Simulation Molecular Dynamics Simulation Humans

A head-to-head comparison of MM/PBSA and MM/GBSA in predicting binding affinities for the CB

Mei Qian Yau, Clarence W Y Liew, Jing Hen Toh et al.
1.00
Receptor, Cannabinoid, CB1 Ligands Molecular Dynamics Simulation Protein Binding Thermodynamics

Motif mapping during chickpea germination reveals a complex sequential activation of different proteolytic activities.

Indrani Bera, Michael O'Sullivan, Caitriona Scaife et al.
1.00
Cicer Germination Proteolysis Seeds Plant Proteins

Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Chromatographie › Chromatographie en phase liquide › Chromatographie sur gel › Evaluation of chemical cross-linkers for...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Chromatographie › Chromatographie en phase liquide › Evaluation of chemical cross-linkers for...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Indicateurs et réactifs › Réactifs réticulants › Evaluation of chemical cross-linkers for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur hormone gastrointestinale › Récepteurs des peptides similaires au glucagon › Récepteur du peptide-1 similaire au glucagon › Evaluation of chemical cross-linkers for...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › Evaluation of chemical cross-linkers for...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de dynamique moléculaire › Evaluation of chemical cross-linkers for...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Evaluation of chemical cross-linkers for...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Stabilité protéique › Evaluation of chemical cross-linkers for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs catécholaminergiques › Récepteurs adrénergiques › Récepteurs alpha-adrénergiques › Récepteurs alpha-2 adrénergiques › Evaluation of chemical cross-linkers for...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Spectrométrie de masse › Spectrométrie de masse en tandem › Evaluation of chemical cross-linkers for...