Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| 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/10362/132801 |
Resumo: | 12/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. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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 AntigenBiochemistrySDG 3 - Good Health and Well-being12/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.The 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.UCIBIO - Applied Molecular Biosciences UnitDQ - Departamento de QuímicaRUNGabba, AdeleBogucka, AgnieszkaLuz, John G.Diniz, AnaCoelho, HelenaCorzana, FranciscoCañada, Francisco JavierMarcelo, FilipaMurphy, Paul V.Birrane, Gabriel2022-02-12T23:27:37Z2021-05-042021-05-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10application/pdfhttp://hdl.handle.net/10362/132801eng0006-2960PURE: 40941467https://doi.org/10.1021/acs.biochem.1c00009info: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:RCAAP2024-03-11T05:11:29Zoai:run.unl.pt:10362/132801Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:47:36.324822Repositório 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 |
Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen |
| title |
Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen |
| spellingShingle |
Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen Gabba, Adele Biochemistry SDG 3 - Good Health and Well-being |
| title_short |
Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen |
| title_full |
Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen |
| title_fullStr |
Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen |
| title_full_unstemmed |
Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen |
| title_sort |
Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen |
| author |
Gabba, Adele |
| author_facet |
Gabba, Adele Bogucka, Agnieszka Luz, John G. Diniz, Ana Coelho, Helena Corzana, Francisco Cañada, Francisco Javier Marcelo, Filipa Murphy, Paul V. Birrane, Gabriel |
| author_role |
author |
| author2 |
Bogucka, Agnieszka Luz, John G. Diniz, Ana Coelho, Helena Corzana, Francisco Cañada, Francisco Javier Marcelo, Filipa Murphy, Paul V. Birrane, Gabriel |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
UCIBIO - Applied Molecular Biosciences Unit DQ - Departamento de Química RUN |
| dc.contributor.author.fl_str_mv |
Gabba, Adele Bogucka, Agnieszka Luz, John G. Diniz, Ana Coelho, Helena Corzana, Francisco Cañada, Francisco Javier Marcelo, Filipa Murphy, Paul V. Birrane, Gabriel |
| dc.subject.por.fl_str_mv |
Biochemistry SDG 3 - Good Health and Well-being |
| topic |
Biochemistry SDG 3 - Good Health and Well-being |
| description |
12/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. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-05-04 2021-05-04T00:00:00Z 2022-02-12T23:27:37Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/132801 |
| url |
http://hdl.handle.net/10362/132801 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
0006-2960 PURE: 40941467 https://doi.org/10.1021/acs.biochem.1c00009 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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10 application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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