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Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b

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  • معلومة اضافية
    • Contributors:
      DQ - Departamento de Química; UCIBIO - Applied Molecular Biosciences Unit
    • الموضوع:
      2023
    • Collection:
      Repositório da Universidade Nova de Lisboa (UNL)
    • نبذة مختصرة :
      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). ; 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 ...
    • ISSN:
      2041-1723
    • Relation:
      info:eu-repo/grantAgreement/EC/H2020/788143/EU; info:eu-repo/grantAgreement/EC/H2020/804236/EU; info:eu-repo/grantAgreement/EC/H2020/956758/EU; info:eu-repo/grantAgreement/EC/H2020/860325/EU; info:eu-repo/grantAgreement/EC/H2020/956544/EU; info:eu-repo/grantAgreement/FCT/Concurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017/PTDC%2FBIA-MIB%2F31028%2F2017/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0140%2F2020/PT; info:eu-repo/grantAgreement/FCT/CEEC IND 3ed/2020.00233.CEECIND%2FCP1586%2FCT0011/PT; info:eu-repo/grantAgreement/FCT/CEEC IND 3ed/2020.03261.CEECIND%2FCP1586%2FCT0012/PT; info:eu-repo/grantAgreement/FCT/OE/2022.11723.BD/PT; PURE: 65213775; PURE UUID: 97d3338c-2539-4186-881c-d0aa7fa61372; Scopus: 85161916854; PubMed: 37311743; PubMedCentral: PMC10264397; ORCID: /0000-0001-5049-8511/work/151367039; http://hdl.handle.net/10362/154850; https://doi.org/10.1038/s41467-023-39119-8
    • الرقم المعرف:
      10.1038/s41467-023-39119-8
    • الدخول الالكتروني :
      http://hdl.handle.net/10362/154850
      https://doi.org/10.1038/s41467-023-39119-8
    • Rights:
      openAccess
    • الرقم المعرف:
      edsbas.6034EFEA