2NAE
Membrane-bound mouse CD28 cytoplasmic tail
Summary for 2NAE
| Entry DOI | 10.2210/pdb2nae/pdb |
| NMR Information | BMRB: 25935 |
| Descriptor | T-cell-specific surface glycoprotein CD28 (1 entity in total) |
| Functional Keywords | cd28, membrane bound protein, bicelle, costimulation, tcr, signaling protein |
| Biological source | Mus musculus (mouse) |
| Cellular location | Membrane; Single-pass type I membrane protein: P31041 |
| Total number of polymer chains | 1 |
| Total formula weight | 5093.79 |
| Authors | |
| Primary citation | Yang, W.,Pan, W.,Chen, S.,Trendel, N.,Jiang, S.,Xiao, F.,Xue, M.,Wu, W.,Peng, Z.,Li, X.,Ji, H.,Liu, X.,Jiang, H.,Wang, H.,Shen, H.,Dushek, O.,Li, H.,Xu, C. Dynamic regulation of CD28 conformation and signaling by charged lipids and ions. Nat.Struct.Mol.Biol., 24:1081-1092, 2017 Cited by PubMed Abstract: CD28 provides an essential costimulatory signal for T cell activation, and its function is critical in antitumor immunity. However, the molecular mechanism of CD28 transmembrane signaling remains elusive. Here we show that the conformation and signaling of CD28 are regulated by two counteractive charged factors, acidic phospholipids and Ca ions. NMR spectroscopy analyses showed that acidic phospholipids can sequester CD28 signaling motifs within the membrane, thereby limiting CD28 basal signaling. T cell receptor (TCR) activation induced an increase in the local Ca concentration around CD28, and Ca directly disrupted CD28-lipid interaction, leading to opening and signaling of CD28. We observed that the TCR, Ca, and CD28 together form a dual-positive-feedback circuit that substantially amplifies T cell signaling and thus increases antigen sensitivity. This work unravels a new regulatory mechanism for CD28 signaling and thus contributes to the understanding of the dependence of costimulation signaling on TCR signaling and the high sensitivity of T cells. PubMed: 29058713DOI: 10.1038/nsmb.3489 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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