8E5S

X-ray structure of the Deinococcus radiodurans Nramp/MntH divalent transition metal transporter WT in an occluded state

8E5S の概要

• エントリーDOI: 10.2210/pdb8e5s/pdb
• 分子名称: Divalent metal cation transporter MntH, SODIUM ION, CHLORIDE ION, ... (7 entities in total)
• 機能のキーワード: membrane protein, divalent transition metal importer, leut fold, nramp family, metal transport
• 由来する生物種: Deinococcus radiodurans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53694.72

構造登録者

Ray, S.,Gaudet, R. (登録日: 2022-08-22, 公開日: 2023-05-03, 最終更新日: 2023-10-25)

主引用文献

Ray, S.,Berry, S.P.,Wilson, E.A.,Zhang, C.H.,Shekhar, M.,Singharoy, A.,Gaudet, R.
High-resolution structures with bound Mn 2+ and Cd 2+ map the metal import pathway in an Nramp transporter.
Elife, 12:-, 2023

PubMed Abstract: Transporters of the Nramp (Natural resistance-associated macrophage protein) family import divalent transition metal ions into cells of most organisms. By supporting metal homeostasis, Nramps prevent diseases and disorders related to metal insufficiency or overload. Previous studies revealed that Nramps take on a LeuT fold and identified the metal-binding site. We present high-resolution structures of (Dra)Nramp in three stable conformations of the transport cycle revealing that global conformational changes are supported by distinct coordination geometries of its physiological substrate, Mn, across conformations, and by conserved networks of polar residues lining the inner and outer gates. In addition, a high-resolution Cd-bound structure highlights differences in how Cd and Mn are coordinated by DraNramp. Complementary metal binding studies using isothermal titration calorimetry with a series of mutated DraNramp proteins indicate that the thermodynamic landscape for binding and transporting physiological metals like Mn is different and more robust to perturbation than for transporting the toxic Cd metal. Overall, the affinity measurements and high-resolution structural information on metal substrate binding provide a foundation for understanding the substrate selectivity of essential metal ion transporters like Nramps.

PubMed: 37039477
DOI: 10.7554/eLife.84006

実験手法

X-RAY DIFFRACTION (2.38 Å)