PXD060303

PXD060303 is an original dataset announced via ProteomeXchange.

Title	Mapping the nanoscale organization of the human cell surface proteome reveals uncharacterized functional associations and surface antigen clusters
Description	The cell surface is a dynamic interface central to immune activation, cell-cell communication, and signal transduction. Despite its functional significance, the spatial organization of cell surface proteins remains poorly understood. High-resolution fluorescence microscopy and proximity labeling have advanced studies of surface protein arrangement, but a systematic analysis of the spatial organization of the complete surface proteome remains unexplored. In this study, we systematically mapped the surface proteome of human T-lymphocytes and B-lymphoblasts using proximity labeling of 85 antigens, identified from over 100 antibodies tested for binding to surface-exposed proteins. These experiments were coupled with an optimized data-independent acquisition (DIA) mass spectrometry workflow to generate a robust dataset. Unsupervised clustering of the resulting interactome revealed functional modules, including well-characterized complexes such as the T-cell receptor and HLA class I/II, alongside novel clusters. Notably, we identified mitochondrial proteins localized to the surface, including the transcription factor TFAM, suggesting previously unappreciated roles for mitochondrial proteins at the plasma membrane. A high-accuracy machine learning classifier predicted over 6,000 surface protein associations, highlighting functional associations such as IL10RBs role as a negative regulator of type I interferon signaling. Spatial modeling of the surface proteome provided insights into protein dispersion patterns, distinguishing widely distributed proteins, such as CD45, from localized antigens, such as CD226. Interestingly, protein distribution appeared independent of abundance, pointing to active mechanisms regulating surface organization. This work provides a comprehensive map of the human surfaceome, offering a resource for exploring the spatial and functional dynamics of the cell membrane proteome.
HostingRepository	MassIVE
AnnounceDate	2025-02-12
AnnouncementXML	Submission_2025-02-12_16:44:31.252.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Brendan Floyd
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl; Acetyl
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-28 20:33:37	ID requested
⏵ 1	2025-02-12 16:44:31	announced

no publication

submitter keyword: Surfaceomics, Membrane, Proximity labeling, DatasetType:Proteomics

Carolyn Bertozzi
contact affiliation	Stanford University
contact email	bertozzi@stanford.edu
lab head
Brendan Floyd
contact affiliation	Stanford University
contact email	bmfloyd@stanford.edu
lab head
Brendan Floyd
contact affiliation	Stanford University
contact email	bmfloyd@stanford.edu
dataset submitter

MassIVE dataset URI

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v09/MSV000096983/