6PGI

Asymmetric functions of a binuclear metal cluster within the transport pathway of the ZIP transition metal transporters

6PGI の概要

• エントリーDOI: 10.2210/pdb6pgi/pdb
• 分子名称: BbZIP, CADMIUM ION (2 entities in total)
• 機能のキーワード: zip, zinc, metal transporter, cadmium, binuclear metal cluster, transport protein
• 由来する生物種: Bordetella bronchiseptica
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31089.05

構造登録者

Zhang, T.,Sui, D.,Zhang, C.,Logan, T.,Hu, J. (登録日: 2019-06-24, 公開日: 2019-12-11, 最終更新日: 2023-10-11)

主引用文献

Zhang, T.,Sui, D.,Zhang, C.,Cole, L.,Hu, J.
Asymmetric functions of a binuclear metal center within the transport pathway of a human zinc transporter ZIP4.
Faseb J., 34:237-247, 2020

PubMed Abstract: Metal clusters are exploited by numerous metalloenzymes for catalysis, but it is not common to utilize a metal cluster for substrate transport across membrane. The recent crystal structure of a prototypic Zrt-/Irt-like protein (ZIP) metal transporter from Bordetella bronchiseptica (BbZIP) revealed an unprecedented binuclear metal center (BMC) within the transport pathway. Here, through a combination of bioinformatics, biochemical and structural approaches, we concluded that the two physically associated metal-binding sites in the BMC of human ZIP4 (hZIP4) zinc transporter exert different functions: one conserved transition metal-binding site acts as the transport site essential for activity, whereas the variable metal-binding site is required for hZIP4's optimal activity presumably by serving as a secondary transport site and modulating the properties of the primary transport site. Sequential soaking experiments on BbZIP crystals clarified the process of metal release from the BMC to the bulky solvent. This work provides important insights into the transport mechanism of the ZIPs broadly involved in transition metal homeostasis and signaling, and also a paradigm on a novel function of metal cluster in metalloproteins.

PubMed: 31914589
DOI: 10.1096/fj.201902043R

実験手法

X-RAY DIFFRACTION (3.5 Å)