PXD049300

PXD049300 is an original dataset announced via ProteomeXchange.

Title	A novel interaction site determines binding between AP180 and AP2 in clathrin mediated endocytosis
Description	The early phases of clathrin mediated endocytosis are organized through a highly complex interaction network mediated by clathrin associated sorting proteins (CLASPs) that comprise long intrinsically disordered regions (IDRs). AP180 is a CLASP exclusively expressed in neurons and comprising a long IDR of around 600 residues, whose function remains partially elusive. Using NMR spectroscopy, we now describe a novel and strong interaction of AP180 with the major adaptor protein AP2 as well as its binding dynamics at atomic resolution. We find that the 70 residue long site determines the overall interaction between AP180 and AP2 in a dynamic equilibrium between its bound and unbound sate, while weaker binding sites contributing to the overall affinity at much high concentrations of AP2. Our data suggest that this novel interaction site might play a central role in recruitment of AP2 to the clathrin coated pit, whereas more transient and promiscuous interactions allow reshaping the interaction network until cargo uptake inside a coated vesicle.
HostingRepository	PRIDE
AnnounceDate	2024-07-16
AnnouncementXML	Submission_2024-07-16_07:25:36.839.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pin-Lian Jiang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Bos taurus (Bovine); NCBI TaxID: 9913; scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-09 06:11:47	ID requested
1	2024-07-04 11:11:48	announced
⏵ 2	2024-07-16 07:25:37	announced	2024-07-16: Updated project metadata.

Naudi-Fabra S, Elena-Real CA, Vedel IM, Tengo M, Motzny K, Jiang PL, Schmieder P, Liu F, Milles S, An extended interaction site determines binding between AP180 and AP2 in clathrin mediated endocytosis. Nat Commun, 15(1):5884(2024) [pubmed]

10.1038/s41467-024-50212-4;

submitter keyword: Extended AP180:AP2β2 interaction, XL-MS

Sigrid Milles
contact affiliation	Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Straße 10, 13125 Berlin, Germany. Université Grenoble Alpes, CNRS, CEA, IBS, F-38000 Grenoble, France.
contact email	milles@fmp-berlin.de
lab head
Pin-Lian Jiang
contact affiliation	Leibniz-Forschungsinstitut für Molekulare Pharmakologie
contact email	jiang@fmp-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049300
     1. Label: PRIDE project
     2. Name: A novel interaction site determines binding between AP180 and AP2 in clathrin mediated endocytosis