9BET
Structure of the human CD33 transmembrane domain
Summary for 9BET
| Entry DOI | 10.2210/pdb9bet/pdb |
| NMR Information | BMRB: 31167 |
| Descriptor | Myeloid cell surface antigen CD33 (1 entity in total) |
| Functional Keywords | siglec, lectin, receptor, cd33, sugar binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 4384.27 |
| Authors | Ulmer, T.S.,Vu, H.N. (deposition date: 2024-04-16, release date: 2025-03-26, Last modification date: 2025-04-09) |
| Primary citation | Vu, H.N.,Situ, A.J.,Dai, X.,Ulmer, T.S. Structure of the CD33 Receptor and Implications for the Siglec Family. Biochemistry, 64:1450-1462, 2025 Cited by PubMed Abstract: In the innate immune system, the CD33 receptor modulates microglial activity. Its downregulation promises to slow Alzheimer's disease, and it is already targeted in blood cancers. The mechanism underlying CD33 signaling is unresolved. Starting from the available crystal structure of its extracellular IgV-IgC1 domains, we have assembled a model of the human CD33 receptor by characterizing the oligomerization and structure of IgC1, transmembrane, and cytosolic domains in solution. IgC1 homodimerizes via intermolecular β-strand pairing and packing. In contrast, the 21-residue transmembrane helix of CD33 appears monomeric and straight, with a conserved thin neck and thick belly appearance followed by a positively charged cytosolic patch. The cytosolic domain is dynamically unstructured. Sequence alignment and AlphaFold models indicate that IgC domains in the family of human Siglecs, to which CD33 belongs, are surprisingly variable. Only Siglec-6 is identified to analogously dimerize via IgC1. Our CD33 structural model suggests that the receptor is not signaling via a monomer-dimer shift. Rather, we propose that, aided but also constrained by dimerization, multivalent ligands may concentrate the receptor transmembrane and cytosolic domains sufficiently to trigger colocalization with an activating kinase. PubMed: 40067740DOI: 10.1021/acs.biochem.4c00864 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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