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PXD042009

PXD042009 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b
DescriptionSialic 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_09:04:01.981.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMikel Azkargorta
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-05 02:37:52ID requested
12023-07-20 13:08:49announced
22023-11-14 09:04:07announced2023-11-14: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: antibody, cancer, molecular recognition., X-ray crystallography, sialic acid, CD11b, T cells, NMR,Siglec-15
Contact List
Felix Elortza
contact affiliationProteomics Service CIC bioGUNE Bizkaia Tec. Park Build. 800 48160 Derio (Spain)
contact emailfelortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliationProteomics Platform CIC bioGUNE
contact emailmazkargorta@cicbiogune.es
dataset submitter
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Dataset FTP location
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PRIDE project URI
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