5hm7: Difference between revisions
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==The Intracellular domain of Butyrophilin 3A1 protein== | ==The Intracellular domain of Butyrophilin 3A1 protein== | ||
<StructureSection load='5hm7' size='340' side='right' caption='[[5hm7]], [[Resolution|resolution]] 1.93Å' scene=''> | <StructureSection load='5hm7' size='340' side='right'caption='[[5hm7]], [[Resolution|resolution]] 1.93Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5hm7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HM7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HM7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5hm7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HM7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HM7 FirstGlance]. <br> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/BT3A1_HUMAN BT3A1_HUMAN]] Plays a role in T-cell activation and in the adaptive immune response. Regulates the proliferation of activated T-cells. Regulates the release of cytokines and IFNG by activated T-cells. Mediates the response of T-cells toward infected and transformed cells that are characterized by high levels of phosphorylated metabolites, such as isopentenyl pyrophosphate.<ref>PMID:21113407</ref> <ref>PMID:21918970</ref> <ref>PMID:22767497</ref> <ref>PMID:22846996</ref> | [[http://www.uniprot.org/uniprot/BT3A1_HUMAN BT3A1_HUMAN]] Plays a role in T-cell activation and in the adaptive immune response. Regulates the proliferation of activated T-cells. Regulates the release of cytokines and IFNG by activated T-cells. Mediates the response of T-cells toward infected and transformed cells that are characterized by high levels of phosphorylated metabolites, such as isopentenyl pyrophosphate.<ref>PMID:21113407</ref> <ref>PMID:21918970</ref> <ref>PMID:22767497</ref> <ref>PMID:22846996</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human Vgamma9Vdelta2 T cells respond to microbial infections as well as certain types of tumors. The key initiators of Vgamma9Vdelta2 activation are small, pyrophosphate-containing molecules called phosphoantigens (pAgs) that are present in infected cells or accumulate intracellularly in certain tumor cells. Recent studies demonstrate that initiation of the Vgamma9Vdelta2 T cell response begins with sensing of pAg via the intracellular domain of the butyrophilin 3A1 (BTN3A1) molecule. However, it is unknown how downstream events can ultimately lead to T cell activation. Here, using NMR spectrometry and molecular dynamics (MD) simulations, we characterize a global conformational change in the B30.2 intracellular domain of BTN3A1 induced by pAg binding. We also reveal by crystallography two distinct dimer interfaces in the BTN3A1 full-length intracellular domain, which are stable in MD simulations. These interfaces lie in close proximity to the pAg-binding pocket and contain clusters of residues that experience major changes of chemical environment upon pAg binding. This suggests that pAg binding disrupts a preexisting conformation of the BTN3A1 intracellular domain. Using a combination of biochemical, structural, and cellular approaches we demonstrate that the extracellular domains of BTN3A1 adopt a V-shaped conformation at rest, and that locking them in this resting conformation without perturbing their membrane reorganization properties diminishes pAg-induced T cell activation. Based on these results, we propose a model in which a conformational change in BTN3A1 is a key event of pAg sensing that ultimately leads to T cell activation. | |||
Phosphoantigen-induced conformational change of butyrophilin 3A1 (BTN3A1) and its implication on Vgamma9Vdelta2 T cell activation.,Gu S, Sachleben JR, Boughter CT, Nawrocka WI, Borowska MT, Tarrasch JT, Skiniotis G, Roux B, Adams EJ Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7311-E7320. doi:, 10.1073/pnas.1707547114. Epub 2017 Aug 14. PMID:28807997<ref>PMID:28807997</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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<div class="pdbe-citations 5hm7" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Adams, E J]] | [[Category: Adams, E J]] | ||
[[Category: Gu, S]] | [[Category: Gu, S]] | ||
