PXD042009-2

PXD042009 is an original dataset announced via ProteomeXchange.

Title	Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b
Description	Sialic acid-binding Ig-like lectin 15 (Siglec-15) is emerging as an immune modulator and target for cancer immunotherapy. However, limited knowledge regarding its mechanism of action and structure, or its binding partners with T cells, restrains the development of drug candidates that could unleash its full therapeutic potential. Here, we determine the crystal structure of Siglec-15 and delineate its binding epitope by co-crystallization with an anti-Siglec-15 blocking antibody. Saturation transfer-difference nuclear magnetic resonance (STD-NMR) spectroscopy assisted with molecular dynamics simulations reveals the binding mode of Siglec-15 to (2,3)- and 2,6)- linked sialic acids and to the cancer-associated sialyl-Tn (STn) glycoform. Binding of Siglec-15 to T cells, which lack STn expression, depends on the presence of (2,3)- and 2,6)- linked sialoglycans. We identify the leukocyte integrin CD11b as a binding partner of Siglec-15 on human T cells. Collectively, these data provide an integrative understanding of the structural features of Siglec-15 and underscore glycosylation as an additional layer of control of T cell responses.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:04:01.981.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-05 02:37:52	ID requested
1	2023-07-20 13:08:49	announced
⏵ 2	2023-11-14 09:04:07	announced	2023-11-14: Updated project metadata.

Lenza MP, Egia-Mendikute L, Anto, ñ, ana-Vildosola A, Soares CO, Coelho H, Corzana F, Bosch A, Manisha P, Quintana JI, Oyenarte I, Unione L, Moure MJ, Azkargorta M, Atxabal U, Sobczak K, Elortza F, Sutherland JD, Barrio R, Marcelo F, Jim, é, nez-Barbero J, Palazon A, Ere, ñ, o-Orbea J, Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b. Nat Commun, 14(1):3496(2023) [pubmed]

submitter keyword: antibody, cancer, molecular recognition., X-ray crystallography, sialic acid, CD11b, T cells, NMR,Siglec-15

Felix Elortza
contact affiliation	Proteomics Service CIC bioGUNE Bizkaia Tec. Park Build. 800 48160 Derio (Spain)
contact email	felortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2023/07/PXD042009

PRIDE project URI

• PRIDE
  1. PXD042009
     1. Label: PRIDE project
     2. Name: Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b