9bet
From Proteopedia
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(New page: '''Unreleased structure''' The entry 9bet is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of the human CD33 transmembrane domain== | |
| + | <StructureSection load='9bet' size='340' side='right'caption='[[9bet]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9bet]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BET FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 21 models</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9bet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bet OCA], [https://pdbe.org/9bet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bet RCSB], [https://www.ebi.ac.uk/pdbsum/9bet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bet ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CD33_HUMAN CD33_HUMAN] Putative adhesion molecule of myelomonocytic-derived cells that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Induces apoptosis in acute myeloid leukemia (in vitro).<ref>PMID:10556798</ref> <ref>PMID:11320212</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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 beta-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. | ||
| - | + | Structure of the CD33 Receptor and Implications for the Siglec Family.,Vu HN, Situ AJ, Dai X, Ulmer TS Biochemistry. 2025 Mar 11. doi: 10.1021/acs.biochem.4c00864. PMID:40067740<ref>PMID:40067740</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9bet" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ulmer TS]] | ||
| + | [[Category: Vu HN]] | ||
Current revision
Structure of the human CD33 transmembrane domain
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