دورية أكاديمية
Galectin-4 Antimicrobial Activity Primarily Occurs Through its C-Terminal Domain.
| العنوان: | Galectin-4 Antimicrobial Activity Primarily Occurs Through its C-Terminal Domain. |
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| المؤلفون: | Jan HM; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Wu SC; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Stowell CJ; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Vallecillo-Zúniga ML; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Paul A; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Patel KR; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Muthusamy S; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Lin HY; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Ayona D; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Jajosky RP; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Varadkar SP; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Nakahara H; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Chan R; Infectious Disease Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Bhave D; Infectious Disease Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Lane WJ; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Yeung MY; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Hollenhorst MA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Rakoff-Nahoum S; Infectious Disease Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Cummings RD; Harvard Glycomics Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA., Arthur CM; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Stowell SR; Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: srstowell@bwh.harvard.edu. |
| المصدر: | Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2024 May; Vol. 23 (5), pp. 100747. Date of Electronic Publication: 2024 Mar 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 101125647 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-9484 (Electronic) Linking ISSN: 15359476 NLM ISO Abbreviation: Mol Cell Proteomics Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Bethesda, MD : American Society for Biochemistry and Molecular Biology, [2002- |
| مواضيع طبية MeSH: | Galectin 4*/metabolism, Humans ; Protein Domains ; Protein Binding ; Protein Multimerization ; Blood Group Antigens/metabolism ; Escherichia coli/metabolism ; Anti-Infective Agents/pharmacology ; ABO Blood-Group System/metabolism ; ABO Blood-Group System/immunology |
| مستخلص: | Although immune tolerance evolved to reduce reactivity with self, it creates a gap in the adaptive immune response against microbes that decorate themselves in self-like antigens. This is particularly apparent with carbohydrate-based blood group antigens, wherein microbes can envelope themselves in blood group structures similar to human cells. In this study, we demonstrate that the innate immune lectin, galectin-4 (Gal-4), exhibits strain-specific binding and killing behavior towards microbes that display blood group-like antigens. Examination of binding preferences using a combination of microarrays populated with ABO(H) glycans and a variety of microbial strains, including those that express blood group-like antigens, demonstrated that Gal-4 binds mammalian and microbial antigens that have features of blood group and mammalian-like structures. Although Gal-4 was thought to exist as a monomer that achieves functional bivalency through its two linked carbohydrate recognition domains, our data demonstrate that Gal-4 forms dimers and that differences in the intrinsic ability of each domain to dimerize likely influences binding affinity. While each Gal-4 domain exhibited blood group-binding activity, the C-terminal domain (Gal-4C) exhibited dimeric properties, while the N-terminal domain (Gal-4N) failed to similarly display dimeric activity. Gal-4C not only exhibited the ability to dimerize but also possessed higher affinity toward ABO(H) blood group antigens and microbes expressing glycans with blood group-like features. Furthermore, when compared to Gal-4N, Gal-4C exhibited more potent antimicrobial activity. Even in the context of the full-length protein, where Gal-4N is functionally bivalent by virtue of Gal-4C dimerization, Gal-4C continued to display higher antimicrobial activity. These results demonstrate that Gal-4 exists as a dimer and exhibits its antimicrobial activity primarily through its C-terminal domain. In doing so, these data provide important insight into key features of Gal-4 responsible for its innate immune activity against molecular mimicry. Competing Interests: Conflict of interest The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | R01 AI171100 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: blood group antigens; galectin-4; host-microbe interactions; microbe microarray; molecular mimicry |
| المشرفين على المادة: | 0 (Galectin 4) 0 (Blood Group Antigens) 0 (Anti-Infective Agents) 0 (ABO Blood-Group System) |
| تواريخ الأحداث: | Date Created: 20240315 Date Completed: 20240525 Latest Revision: 20240603 |
| رمز التحديث: | 20240603 |
| مُعرف محوري في PubMed: | PMC11097083 |
| DOI: | 10.1016/j.mcpro.2024.100747 |
| PMID: | 38490531 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1535-9484 |
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| DOI: | 10.1016/j.mcpro.2024.100747 |