PXD075032

PXD075032 is an original dataset announced via ProteomeXchange.

Title	Library-Based, Multiplexed Strategy for Mapping Protein Interaction Networks via Crosslinking
Description	Protein-protein interactions are fundamental to cellular function, yet resolving their interaction interfaces and dynamic behaviors in native biological contexts remains challenging, particularly for weak or transient interactions. Crosslinking strategies based on noncanonical amino acids offer an effective means to capture such interactions; however, traditional single-site incorporation provides limited coverage and may overlook critical interaction hotspots.By employing a mutagenesis library, multiple interaction partners and cross-linking sites of a target protein can be simultaneously screened in a single experiment, without prior knowledge of its precise structural or functional features, enabling effective and unbiased analysis of its interaction network. In this study, we constructed an amber codon-scanning mutagenesis library of PSMD10, facilitating independent incorporation of the photocrosslinking ncAA p-azido-phenylalanine at multiple distinct residues. This approach allowed us to systematically interrogate and precisely map potential interaction regions across the protein surface. Coupled with crosslinking mass spectrometry, we identified multiple residues involved in intermolecular interactions, as well as previously unreported interaction partners, including T2FA, TBA1C, and ATRIP. These findings expand our understanding of PSMD10-associated proteasome interactome, demonstrate a multiplexed strategy for in situ mapping of protein interaction interfaces with broad coverage, and offer a valuable platform for developing therapeutics that target protein-protein interactions.
HostingRepository	iProX
AnnounceDate	2026-02-28
AnnouncementXML	Submission_2026-02-27_23:12:13.628.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dongxin Zhao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-27 23:11:57	ID requested
⏵ 1	2026-02-27 23:12:14	announced

Dataset with its publication pending

submitter keyword: Scanning mutagenesis library, Protein-protein interactions, Amber codon scanning, Photo-crosslinking, Crosslinking mass spectrometry

Song Chen
contact affiliation	Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge
contact email	sc43@sanger.ac.uk
lab head
Dongxin Zhao
contact affiliation	Shanghai Institute of Materia Medica, Chinese Academy of Sciences
contact email	zhaodongxin@simm.ac.cn
dataset submitter

iProX dataset URI