View source for 2nae


==Membrane-bound mouse CD28 cytoplasmic tail==
<StructureSection load='2nae' size='340' side='right'caption='[[2nae]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2nae]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NAE FirstGlance]. <br>
</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=2nae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nae OCA], [https://pdbe.org/2nae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nae RCSB], [https://www.ebi.ac.uk/pdbsum/2nae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nae ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CD28_MOUSE CD28_MOUSE] Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation.[UniProtKB:P10747]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 Ca2+ 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 Ca2+ concentration around CD28, and Ca2+ directly disrupted CD28-lipid interaction, leading to opening and signaling of CD28. We observed that the TCR, Ca2+, 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.

Dynamic regulation of CD28 conformation and signaling by charged lipids and ions.,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 Nat Struct Mol Biol. 2017 Oct 23. doi: 10.1038/nsmb.3489. PMID:29058713<ref>PMID:29058713</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2nae" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Li H]]
[[Category: Pan W]]
[[Category: Xu C]]