6RS2

Structure of the Bateman module of human CNNM4.

「4IY3」から置き換えられました

6RS2 の概要

• エントリーDOI: 10.2210/pdb6rs2/pdb
• 関連するPDBエントリー: 6G52
• 分子名称: Metal transporter CNNM4 (1 entity in total)
• 機能のキーワード: cyclin m4, acdp4, magnesium, transporter, jalili syndrome, magnesium absorption, magnesium homeostasis, metal transport, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 70552.20

構造登録者

Corral-Rodriguez, M.A.,Stuiver, M.,Gomez-Garcia, I.,Oyenarte, I.,Gimenez, P.,Ereno-Orbea, J.,Diercks, T.,Muller, D.,Martinez-Cruz, L.A. (登録日: 2019-05-21, 公開日: 2020-07-15, 最終更新日: 2024-01-24)

主引用文献

Gimenez-Mascarell, P.,Oyenarte, I.,Gonzalez-Recio, I.,Fernandez-Rodriguez, C.,Corral-Rodriguez, M.A.,Campos-Zarraga, I.,Simon, J.,Kostantin, E.,Hardy, S.,Diaz Quintana, A.,Zubillaga Lizeaga, M.,Merino, N.,Diercks, T.,Blanco, F.J.,Diaz Moreno, I.,Martinez-Chantar, M.L.,Tremblay, M.L.,Muller, D.,Siliqi, D.,Martinez-Cruz, L.A.
Structural Insights into the Intracellular Region of the Human Magnesium Transport Mediator CNNM4.
Int J Mol Sci, 20:-, 2019

PubMed Abstract: The four member family of "Cyclin and Cystathionine β-synthase (CBS) domain divalent metal cation transport mediators", CNNMs, are the least-studied mammalian magnesium transport mediators. CNNM4 is abundant in the brain and the intestinal tract, and its abnormal activity causes Jalili Syndrome. Recent findings show that suppression of CNNM4 in mice promotes malignant progression of intestinal polyps and is linked to infertility. The association of CNNM4 with phosphatases of the regenerating liver, PRLs, abrogates its Mg-efflux capacity, thus resulting in an increased intracellular Mg concentration that favors tumor growth. Here we present the crystal structures of the two independent intracellular domains of human CNNM4, i.e., the Bateman module and the cyclic nucleotide binding-like domain (cNMP). We also derive a model structure for the full intracellular region in the absence and presence of MgATP and the oncogenic interacting partner, PRL-1. We find that only the Bateman module interacts with ATP and Mg, at non-overlapping sites facilitating their positive cooperativity. Furthermore, both domains dimerize autonomously, where the cNMP domain dimer forms a rigid cleft to restrict the Mg induced sliding of the inserting CBS1 motives of the Bateman module, from a twisted to a flat disk shaped dimer.

PubMed: 31842432
DOI: 10.3390/ijms20246279

実験手法

X-RAY DIFFRACTION (3.694 Å)