Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/154850 |
Resumo: | Funding Information: X-ray diffraction experiments described in this paper were performed using beamlines XALOC synchrotron at ALBA (Spain) and PXIII in Swiss Light Source (Switzerland). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 22161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). F.M. and J.J.-B. acknowledge to the European funding for the GLYCOTwinning project (No. 101079417) and -COST Action GLYCONANOPROBES. A.P.’s research is funded by “La Caixa” Foundation (HR21-00925), AECC (LABAE211744PALA), Fundación FERO, Ikerbasque, and BIOEF EITB MARATOIA BIO19/CP/002. We thank Agencia Estatal de Investigación of Spain for grants PID2019-107956RA-I00 (A.P.), PID2019-107770RA-I00 (J.E.-O.), RTI2018-099592-B-C21 (F.C.), ID2020-114178GB (R.B. and J.D.S.), RYC2018-024183-I (A.P.), and the Severo Ochoa Center of Excellence Accreditation CEX2021-001136-S, all funded by MCIN/AEI/10.13039/501100011033 and by El FSE invierte en tu futuro, as well as CIBERES, and initiative of Instituto de Salud Carlos III (ISCIII, Spain) A.A.-V. receives funding from “La Caixa” Foundation (ID 100010434, LCF/BQ/DR20/11790022). A. B. (AECC Bizkaia Scientific Foundation, PRDVZ19003BOSC). F.C. acknowledges the Mizutani Foundation for Glycoscience (Grant 220115). Publisher Copyright: © 2023, The Author(s). |
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Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11bChemistry(all)Biochemistry, Genetics and Molecular Biology(all)Physics and Astronomy(all)SDG 3 - Good Health and Well-beingFunding Information: X-ray diffraction experiments described in this paper were performed using beamlines XALOC synchrotron at ALBA (Spain) and PXIII in Swiss Light Source (Switzerland). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 22161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). F.M. and J.J.-B. acknowledge to the European funding for the GLYCOTwinning project (No. 101079417) and -COST Action GLYCONANOPROBES. A.P.’s research is funded by “La Caixa” Foundation (HR21-00925), AECC (LABAE211744PALA), Fundación FERO, Ikerbasque, and BIOEF EITB MARATOIA BIO19/CP/002. We thank Agencia Estatal de Investigación of Spain for grants PID2019-107956RA-I00 (A.P.), PID2019-107770RA-I00 (J.E.-O.), RTI2018-099592-B-C21 (F.C.), ID2020-114178GB (R.B. and J.D.S.), RYC2018-024183-I (A.P.), and the Severo Ochoa Center of Excellence Accreditation CEX2021-001136-S, all funded by MCIN/AEI/10.13039/501100011033 and by El FSE invierte en tu futuro, as well as CIBERES, and initiative of Instituto de Salud Carlos III (ISCIII, Spain) A.A.-V. receives funding from “La Caixa” Foundation (ID 100010434, LCF/BQ/DR20/11790022). A. B. (AECC Bizkaia Scientific Foundation, PRDVZ19003BOSC). F.C. acknowledges the Mizutani Foundation for Glycoscience (Grant 220115). Publisher Copyright: © 2023, The Author(s).Sialic acid-binding Ig-like lectin 15 (Siglec-15) is an immune modulator and emerging cancer immunotherapy target. However, limited understanding of its structure and mechanism of action restrains the development of drug candidates that unleash its full therapeutic potential. In this study, we elucidate the crystal structure of Siglec-15 and its binding epitope via co-crystallization with an anti-Siglec-15 blocking antibody. Using saturation transfer-difference nuclear magnetic resonance (STD-NMR) spectroscopy and molecular dynamics simulations, we reveal Siglec-15 binding mode to α(2,3)- and α(2,6)-linked sialic acids and the cancer-associated sialyl-Tn (STn) glycoform. We demonstrate that binding of Siglec-15 to T cells, which lack STn expression, depends on the presence of α(2,3)- and α(2,6)-linked sialoglycans. Furthermore, we identify the leukocyte integrin CD11b as a Siglec-15 binding partner on human T cells. Collectively, our findings provide an integrated understanding of the structural features of Siglec-15 and emphasize glycosylation as a crucial factor in controlling T cell responses.DQ - Departamento de QuímicaUCIBIO - Applied Molecular Biosciences UnitRUNLenza, Maria PiaEgia-Mendikute, LeireAntoñana-Vildosola, AsierSoares, Cátia O.Coelho, HelenaCorzana, FranciscoBosch, AlexandreManisha, ProdhiQuintana, Jon ImanolOyenarte, IkerUnione, LucaMoure, María JesúsAzkargorta, MikelAtxabal, UnaiSobczak, KlaudiaElortza, FelixSutherland, James D.Barrio, RosaMarcelo, FilipaJiménez-Barbero, JesúsPalazon, AsisEreño-Orbea, June2023-07-04T22:18:34Z2023-122023-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article14application/pdfhttp://hdl.handle.net/10362/154850eng2041-1723PURE: 65213775https://doi.org/10.1038/s41467-023-39119-8info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:37:19Zoai:run.unl.pt:10362/154850Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:55:47.673059Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b |
title |
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b |
spellingShingle |
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b Lenza, Maria Pia Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) SDG 3 - Good Health and Well-being |
title_short |
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b |
title_full |
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b |
title_fullStr |
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b |
title_full_unstemmed |
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b |
title_sort |
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b |
author |
Lenza, Maria Pia |
author_facet |
Lenza, Maria Pia Egia-Mendikute, Leire Antoñana-Vildosola, Asier Soares, Cátia O. Coelho, Helena Corzana, Francisco Bosch, Alexandre Manisha, Prodhi Quintana, Jon Imanol Oyenarte, Iker Unione, Luca Moure, María Jesús Azkargorta, Mikel Atxabal, Unai Sobczak, Klaudia Elortza, Felix Sutherland, James D. Barrio, Rosa Marcelo, Filipa Jiménez-Barbero, Jesús Palazon, Asis Ereño-Orbea, June |
author_role |
author |
author2 |
Egia-Mendikute, Leire Antoñana-Vildosola, Asier Soares, Cátia O. Coelho, Helena Corzana, Francisco Bosch, Alexandre Manisha, Prodhi Quintana, Jon Imanol Oyenarte, Iker Unione, Luca Moure, María Jesús Azkargorta, Mikel Atxabal, Unai Sobczak, Klaudia Elortza, Felix Sutherland, James D. Barrio, Rosa Marcelo, Filipa Jiménez-Barbero, Jesús Palazon, Asis Ereño-Orbea, June |
author2_role |
author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
DQ - Departamento de Química UCIBIO - Applied Molecular Biosciences Unit RUN |
dc.contributor.author.fl_str_mv |
Lenza, Maria Pia Egia-Mendikute, Leire Antoñana-Vildosola, Asier Soares, Cátia O. Coelho, Helena Corzana, Francisco Bosch, Alexandre Manisha, Prodhi Quintana, Jon Imanol Oyenarte, Iker Unione, Luca Moure, María Jesús Azkargorta, Mikel Atxabal, Unai Sobczak, Klaudia Elortza, Felix Sutherland, James D. Barrio, Rosa Marcelo, Filipa Jiménez-Barbero, Jesús Palazon, Asis Ereño-Orbea, June |
dc.subject.por.fl_str_mv |
Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) SDG 3 - Good Health and Well-being |
topic |
Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) SDG 3 - Good Health and Well-being |
description |
Funding Information: X-ray diffraction experiments described in this paper were performed using beamlines XALOC synchrotron at ALBA (Spain) and PXIII in Swiss Light Source (Switzerland). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 22161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). F.M. and J.J.-B. acknowledge to the European funding for the GLYCOTwinning project (No. 101079417) and -COST Action GLYCONANOPROBES. A.P.’s research is funded by “La Caixa” Foundation (HR21-00925), AECC (LABAE211744PALA), Fundación FERO, Ikerbasque, and BIOEF EITB MARATOIA BIO19/CP/002. We thank Agencia Estatal de Investigación of Spain for grants PID2019-107956RA-I00 (A.P.), PID2019-107770RA-I00 (J.E.-O.), RTI2018-099592-B-C21 (F.C.), ID2020-114178GB (R.B. and J.D.S.), RYC2018-024183-I (A.P.), and the Severo Ochoa Center of Excellence Accreditation CEX2021-001136-S, all funded by MCIN/AEI/10.13039/501100011033 and by El FSE invierte en tu futuro, as well as CIBERES, and initiative of Instituto de Salud Carlos III (ISCIII, Spain) A.A.-V. receives funding from “La Caixa” Foundation (ID 100010434, LCF/BQ/DR20/11790022). A. B. (AECC Bizkaia Scientific Foundation, PRDVZ19003BOSC). F.C. acknowledges the Mizutani Foundation for Glycoscience (Grant 220115). Publisher Copyright: © 2023, The Author(s). |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-04T22:18:34Z 2023-12 2023-12-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/154850 |
url |
http://hdl.handle.net/10362/154850 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2041-1723 PURE: 65213775 https://doi.org/10.1038/s41467-023-39119-8 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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14 application/pdf |
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RCAAP |
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