6AVJ

Crystal structure of human Mitochondrial inner NEET protein (MiNT)/CISD3

6AVJ の概要

• エントリーDOI: 10.2210/pdb6avj/pdb
• 分子名称: CDGSH iron-sulfur domain-containing protein 3, mitochondrial, FE2/S2 (INORGANIC) CLUSTER (3 entities in total)
• 機能のキーワード: neet-fold, iron-sulfur cluster, mitochondria, metal binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 31709.08

構造登録者

Lipper, C.H.,Karmi, O.,Sohn, Y.S.,Darash-Yahana, M.,Lammert, H.,Song, L.,Liu, A.,Mittler, R.,Nechushtai, R.,Onuchic, J.N.,Jennings, P.A. (登録日: 2017-09-02, 公開日: 2017-12-20, 最終更新日: 2023-10-04)

主引用文献

Lipper, C.H.,Karmi, O.,Sohn, Y.S.,Darash-Yahana, M.,Lammert, H.,Song, L.,Liu, A.,Mittler, R.,Nechushtai, R.,Onuchic, J.N.,Jennings, P.A.
Structure of the human monomeric NEET protein MiNT and its role in regulating iron and reactive oxygen species in cancer cells.
Proc. Natl. Acad. Sci. U.S.A., 115:272-277, 2018

PubMed Abstract: The NEET family is a relatively new class of three related [2Fe-2S] proteins (CISD1-3), important in human health and disease. While there has been growing interest in the homodimeric gene products of CISD1 (mitoNEET) and CISD2 (NAF-1), the importance of the inner mitochondrial CISD3 protein has only recently been recognized in cancer. The CISD3 gene encodes for a monomeric protein that contains two [2Fe-2S] CDGSH motifs, which we term mitochondrial inner NEET protein (MiNT). It folds with a pseudosymmetrical fold that provides a hydrophobic motif on one side and a relatively hydrophilic surface on the diametrically opposed surface. Interestingly, as shown by molecular dynamics simulation, the protein displays distinct asymmetrical backbone motions, unlike its homodimeric counterparts that face the cytosolic side of the outer mitochondrial membrane/endoplasmic reticulum (ER). However, like its counterparts, our biological studies indicate that knockdown of MiNT leads to increased accumulation of mitochondrial labile iron, as well as increased mitochondrial reactive oxygen production. Taken together, our study suggests that the MiNT protein functions in the same pathway as its homodimeric counterparts (mitoNEET and NAF-1), and could be a key player in this pathway within the mitochondria. As such, it represents a target for anticancer or antidiabetic drug development.

PubMed: 29259115
DOI: 10.1073/pnas.1715842115

実験手法

X-RAY DIFFRACTION (1.9 Å)