The cryo-EM structure of the endocytic receptor DEC-205
| Autor: | William R. Heath, Hariprasad Venugopal, Carmen Llerena, Felix A. Deuss, Irina Caminschi, Richard Berry, Zhihui Fu, Alex J. Fulcher, Jessica Li, Benjamin S. Gully, Mireille H. Lahoud, Jamie Rossjohn |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Protein family dendritic cell Protein Conformation SEC-MALS size exclusion–coupled multiangle light scattering Endocytic cycle cryo-electron microscopy Receptors Cell Surface Ligands Biochemistry oligomerization immunology Minor Histocompatibility Antigens 03 medical and health sciences Protein structure FNII fibronectin type II Tetramer Antigens CD Humans membrane protein Lectins C-Type CTLDs C-type lectin-like domains Receptor Molecular Biology receptor structure function CysR cysteine-rich 030102 biochemistry & molecular biology Chemistry Oligonucleotide CpG cytosine–guanosine Cryoelectron Microscopy Editors' Pick Cell Biology MR mannose receptor PLA2R M-type phospholipase A2 receptor Fibronectins Cell biology 030104 developmental biology eGFP enhanced green fluorescent protein Membrane protein receptor endocytosis SV-AUC sedimentation velocity analytical ultracentrifugation ECDs ectodomains DCs dendritic cells Mannose receptor Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra120.016451 |
| Popis: | DEC-205 (CD205), a member of the macrophage mannose receptor protein family, is the prototypic endocytic receptor of dendritic cells, whose ligands include phosphorothioated cytosine-guanosine oligonucleotides, a motif often seen in bacterial or viral DNA. However, despite growing biological and clinical significance, little is known about the structural arrangement of this receptor or any of its family members. Here, we describe the 3.2 Å cryo-EM structure of human DEC-205, thereby illuminating the structure of the mannose receptor protein family. The DEC-205 monomer forms a compact structure comprising two intercalated rings of C-type lectin-like domains, where the N-terminal cysteine-rich and fibronectin domains reside at the central intersection. We establish a pH-dependent oligomerization pathway forming tetrameric DEC-205 using solution-based techniques and ultimately solved the 4.9 Å cryo-EM structure of the DEC-205 tetramer to identify the unfurling of the second lectin ring which enables tetramer formation. Furthermore, we suggest the relevance of this oligomerization pathway within a cellular setting, whereby cytosine-guanosine binding appeared to disrupt this cell-surface oligomer. Accordingly, we provide insight into the structure and oligomeric assembly of the DEC-205 receptor. |
| Databáze: | OpenAIRE |
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