PXD048942

PXD048942 is an original dataset announced via ProteomeXchange.

Title	Structural mass spectrometry captures residue-resolved comprehensive conformational rearrangements of a G protein-coupled receptor
Description	GPCR structural studies with in-solution spectroscopic approaches have offered distinctive insights into GPCR activation and signaling that highly complement those yielded from structural snapshots by crystallography or cryo-EM. While most current spectroscopic approaches excel at probing structural changes at selected residues or loop regions, they are not suitable for capturing a holistic view of GPCR conformational rearrangements across multiple domains. Herein, we develop an approach based on limited proteolysis mass spectrometry (LiP-MS) to simultaneously monitor conformational alterations of a large number of residues spanning both flexible loops and structured transmembrane domains for a given GPCR. To benchmark LiP-MS for GPCR conformational profiling, we studied adenosine 2A receptor (A2AR) in response to different ligand binding (agonist/antagonist/allosteric modulators) and G protein coupling. Systematic and residue-resolved profiling of A2AR conformational rearrangements by LiP-MS precisely captures structural mechanisms in multiple domains underlying ligand engagement, receptor activation and allostery, and may also reflect local conformational flexibility. Furthermore, these residue-resolution structural fingerprints of A2AR protein allow us to readily classify ligands of different pharmacology and distinguish the G protein-coupled state. Thus, we establish a new structural MS approach that would help address ligand or transducer-induced conformational transition and plasticity, a long-standing challenge for GPCR biology and rational drug design.
HostingRepository	iProX
AnnounceDate	2024-04-26
AnnouncementXML	Submission_2024-07-17_00:04:18.750.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hongyue Liu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-28 18:02:56	ID requested
⏵ 1	2024-07-17 00:04:19	announced

Liu H, Yan P, Zhang Z, Han H, Zhou Q, Zheng J, Zhang J, Xu F, Shui W, Structural Mass Spectrometry Captures Residue-Resolved Comprehensive Conformational Rearrangements of a G Protein-Coupled Receptor. J Am Chem Soc, 146(29):20045-20058(2024) [pubmed]

submitter keyword: GPCR, LiP-MS, structural mass spectrometry, adenosing 2A receptor

Wenqing Shui
contact affiliation	iHuman Institute
contact email	shuiwq@shanghaitech.edu.cn
lab head
Hongyue Liu
contact affiliation	ShanghaiTech University
contact email	liuhy5@shanghaitech.edu.cn
dataset submitter

iProX dataset URI