PXD036220-1

PXD036220 is an original dataset announced via ProteomeXchange.

Title	Structural and functional studies of CC chemokine receptor 5 phosphorylation and its interactions with arrestin2
Description	The two non-visual arrestin isoforms, arrestin2 and arrestin3, recognize and bind hundreds of G protein-coupled receptors (GPCRs) with different phosphorylation patterns leading to distinct functional outcomes. Whereas the impact of phosphorylation of the vasopressin 2 receptor and rhodopsin on arrestin interactions has been well studied, much less known for other GPCRs. Here we have characterized the interaction between the phosphorylated CC chemokine receptor 5 (CCR5) and arrestin2. Mass spectrometry and biochemical revealed several new CCR5 phosphorylation sites, which proved essential for the formation of stable complexes with arrestin2. Crystal structures of arrestin2 in apo form and in complexes with two CCR5 C-terminal phosphopeptides revealed three key CCR5 phosphoresidues in a pXpp motif that form extensive interactions with arrestin2 and lead to activation. The same phosphoresidue-cluster is present in other receptors which form stable complexes with arrestin2. The contributions of each CCR5 phosphoresidue on arrestin2 conformation and binding have been characterized by a combination of NMR spectroscopy, biochemical and functional assays. We propose that the identified pXpp motif is responsible for robust arrestin2 recruitment in many GPCRs. Moreover, an analysis of available sequence, structural and functional information on other GPCR arrestin interactions suggests a particular spatial arrangement of phosphoresidues within the GPCR intracellular loops and C-terminal tail determines arrestin2 and 3 isoform specificity.
HostingRepository	PRIDE
AnnounceDate	2023-05-24
AnnouncementXML	Submission_2023-05-24_07:52:27.173.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD036220
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	AlexanderSchmidt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-22 03:46:36	ID requested
⏵ 1	2023-05-24 07:52:27	announced
2	2023-11-14 08:57:51	announced	2023-11-14: Updated project metadata.

10.6019/PXD036220;

submitter keyword: PO4

AlexSchmidt
contact affiliation	Biozentrum, University of basel, CH
contact email	alex.schmidt@unibas.ch
lab head
AlexanderSchmidt
contact affiliation	Proteomics Core Facility
contact email	alex.schmidt@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036220
     1. Label: PRIDE project
     2. Name: Structural and functional studies of CC chemokine receptor 5 phosphorylation and its interactions with arrestin2