9b9g: Difference between revisions
m Protected "9b9g" [edit=sysop:move=sysop] |
No edit summary |
||
| Line 1: | Line 1: | ||
The entry | ==Structure of the PI4KA complex bound to Calcineurin== | ||
<StructureSection load='9b9g' size='340' side='right'caption='[[9b9g]], [[Resolution|resolution]] 3.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9b9g]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9B9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9B9G FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5Å</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=9b9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9b9g OCA], [https://pdbe.org/9b9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9b9g RCSB], [https://www.ebi.ac.uk/pdbsum/9b9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9b9g ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PI4KA_HUMAN PI4KA_HUMAN] Combined immunodeficiency-enteropathy spectrum;Autosomal recessive spastic paraplegia type 84;Bilateral perisylvian polymicrogyria. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PI4KA_HUMAN PI4KA_HUMAN] Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate.<ref>PMID:10101268</ref> <ref>PMID:23229899</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Phosphatidylinositol 4-kinase alpha (PI4KA) maintains the phosphatidylinositol 4-phosphate (PI4P) and phosphatidylserine pools of the plasma membrane. A key regulator of PI4KA is its association into a complex with TTC7 and FAM126 proteins. This complex can be regulated by the CNAbeta1 isoform of the phosphatase calcineurin. We previously identified that CNAbeta1 directly binds to FAM126A. Here, we report a cryoelectron microscopic (cryo-EM) structure of a truncated PI4KA complex bound to calcineurin, revealing a unique direct interaction between PI4KA and calcineurin. Hydrogen deuterium exchange mass spectrometry (HDX-MS) and computational analysis show that calcineurin forms a complex with an evolutionarily conserved IKISVT sequence in PI4KA's horn domain. We also characterized conserved LTLT and PSISIT calcineurin binding sequences in the C terminus of FAM126A. These dual sites in PI4KA and FAM126A are both in close proximity to phosphorylation sites in the PI4KA complex, suggesting key roles of calcineurin-regulated phosphosites in PI4KA regulation. This work reveals novel insight into how calcineurin can regulate PI4KA activity. | |||
Structure of calcineurin bound to PI4KA reveals dual interface in both PI4KA and FAM126A.,Shaw AL, Suresh S, Parson MAH, Harris NJ, Jenkins ML, Yip CK, Burke JE Structure. 2024 Aug 22:S0969-2126(24)00324-1. doi: 10.1016/j.str.2024.08.007. PMID:39216471<ref>PMID:39216471</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9b9g" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Burke JE]] | |||
[[Category: Shaw AL]] | |||
[[Category: Suresh S]] | |||
[[Category: Yip CK]] | |||
Latest revision as of 09:12, 11 September 2024
Structure of the PI4KA complex bound to CalcineurinStructure of the PI4KA complex bound to Calcineurin
Structural highlights
DiseasePI4KA_HUMAN Combined immunodeficiency-enteropathy spectrum;Autosomal recessive spastic paraplegia type 84;Bilateral perisylvian polymicrogyria. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionPI4KA_HUMAN Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate.[1] [2] Publication Abstract from PubMedPhosphatidylinositol 4-kinase alpha (PI4KA) maintains the phosphatidylinositol 4-phosphate (PI4P) and phosphatidylserine pools of the plasma membrane. A key regulator of PI4KA is its association into a complex with TTC7 and FAM126 proteins. This complex can be regulated by the CNAbeta1 isoform of the phosphatase calcineurin. We previously identified that CNAbeta1 directly binds to FAM126A. Here, we report a cryoelectron microscopic (cryo-EM) structure of a truncated PI4KA complex bound to calcineurin, revealing a unique direct interaction between PI4KA and calcineurin. Hydrogen deuterium exchange mass spectrometry (HDX-MS) and computational analysis show that calcineurin forms a complex with an evolutionarily conserved IKISVT sequence in PI4KA's horn domain. We also characterized conserved LTLT and PSISIT calcineurin binding sequences in the C terminus of FAM126A. These dual sites in PI4KA and FAM126A are both in close proximity to phosphorylation sites in the PI4KA complex, suggesting key roles of calcineurin-regulated phosphosites in PI4KA regulation. This work reveals novel insight into how calcineurin can regulate PI4KA activity. Structure of calcineurin bound to PI4KA reveals dual interface in both PI4KA and FAM126A.,Shaw AL, Suresh S, Parson MAH, Harris NJ, Jenkins ML, Yip CK, Burke JE Structure. 2024 Aug 22:S0969-2126(24)00324-1. doi: 10.1016/j.str.2024.08.007. PMID:39216471[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||