9B9G

Structure of the PI4KA complex bound to Calcineurin

9B9G の概要

• エントリーDOI: 10.2210/pdb9b9g/pdb
• EMDBエントリー: 44382
• 分子名称: Phosphatidylinositol 4-kinase alpha, Tetratricopeptide repeat protein 7B, Hyccin, ... (6 entities in total)
• 機能のキーワード: pi4kiiia complex, pi4ka, ttc7b, fam126a, cna, cnb, calcineurin, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 912803.43

構造登録者

Shaw, A.L.,Suresh, S.,Yip, C.K.,Burke, J.E. (登録日: 2024-04-02, 公開日: 2024-09-11, 最終更新日: 2025-05-28)

主引用文献

Shaw, A.L.,Suresh, S.,Parson, M.A.H.,Harris, N.J.,Jenkins, M.L.,Yip, C.K.,Burke, J.E.
Structure of calcineurin bound to PI4KA reveals dual interface in both PI4KA and FAM126A.
Structure, 32:1973-, 2024

PubMed Abstract: 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 CNAβ1 isoform of the phosphatase calcineurin. We previously identified that CNAβ1 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.

PubMed: 39216471
DOI: 10.1016/j.str.2024.08.007

実験手法

ELECTRON MICROSCOPY (3.5 Å)