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Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen

2021-05-04Artigo científico Acesso aberto
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dc.contributor.authorGabba, Adele
dc.contributor.authorBogucka, Agnieszka
dc.contributor.authorLuz, John G.
dc.contributor.authorDiniz, Ana
dc.contributor.authorCoelho, Helena
dc.contributor.authorCorzana, Francisco
dc.contributor.authorCañada, Francisco Javier
dc.contributor.authorMarcelo, Filipa
dc.contributor.authorMurphy, Paul V.
dc.contributor.authorBirrane, Gabriel
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.pblACS - American Chemical Society
dc.date.accessioned2022-02-12T23:27:37Z
dc.date.available2022-02-12T23:27:37Z
dc.date.issued2021-05-04
dc.description12/IA/1398 16/IA/4419 GOIPG/2016/858 IF/00780/2015 PTDC/BIA-MIB/31028/2017 UIDB/04378/2020 PD/BD/142847/2018 RTI2018-094751-B-C22 RTI2018-099592-B-C2.
dc.description.abstractThe human macrophage galactose lectin (MGL) is an endocytic type II transmembrane receptor expressed on immature monocyte-derived dendritic cells and activated macrophages and plays a role in modulating the immune system in response to infections and cancer. MGL contains an extracellular calcium-dependent (C-type) carbohydrate recognition domain (CRD) that specifically binds terminal N-acetylgalactosamine glycan residues such as the Tn and sialyl-Tn antigens found on tumor cells, as well as other N- and O-glycans displayed on certain viruses and parasites. Even though the glycan specificity of MGL is known and several binding glycoproteins have been identified, the molecular basis for substrate recognition has remained elusive due to the lack of high-resolution structures. Here we present crystal structures of the MGL CRD at near endosomal pH and in several complexes, which reveal details of the interactions with the natural ligand, GalNAc, the cancer-associated Tn-Ser antigen, and a synthetic GalNAc mimetic ligand. Like the asialoglycoprotein receptor, additional calcium atoms are present and contribute to stabilization of the MGL CRD fold. The structure provides the molecular basis for preferential binding of N-acetylgalactosamine over galactose and prompted the re-evaluation of the binding modes previously proposed in solution. Saturation transfer difference nuclear magnetic resonance data acquired using the MGL CRD and interpreted using the crystal structure indicate a single binding mode for GalNAc in solution. Models of MGL1 and MGL2, the mouse homologues of MGL, explain how these proteins might recognize LewisX and GalNAc, respectively.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent10
dc.format.extent3072670
dc.identifier.doi10.1021/acs.biochem.1c00009
dc.identifier.issn0006-2960
dc.identifier.otherPURE: 40941467
dc.identifier.otherPURE UUID: 6a948520-fcf2-4200-926d-fa77675d7b2e
dc.identifier.otherScopus: 85103508032
dc.identifier.otherPubMed: 33724805
dc.identifier.otherWOS: 000648509400002
dc.identifier.otherORCID: /0000-0001-5049-8511/work/108073952
dc.identifier.urihttp://hdl.handle.net/10362/132801
dc.identifier.urlhttps://www.scopus.com/pages/publications/85103508032
dc.language.isoeng
dc.peerreviewedyes
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/221613/EU
dc.relationProneural mechanisms coupling cell cycle exit and differentiation
dc.subjectBiochemistry
dc.subjectSDG 3 - Good Health and Well-being
dc.titleCrystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigenen
dc.typejournal article
degois.publication.firstPage1327
degois.publication.issue17
degois.publication.lastPage1336
degois.publication.titleBiochemistry
degois.publication.volume60
dspace.entity.typePublication
oaire.awardNumber221613
oaire.awardTitleProneural mechanisms coupling cell cycle exit and differentiation
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/221613/EU
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccess
relation.isProjectOfPublicationf5805d1b-851a-46dd-9695-a0b9a3ab6723
relation.isProjectOfPublication.latestForDiscoveryf5805d1b-851a-46dd-9695-a0b9a3ab6723

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