8YR3

Cryo-EM structure of the human ABCB6 in complex with Cd(II):GSH

8YR3 の概要

• エントリーDOI: 10.2210/pdb8yr3/pdb
• 関連するPDBエントリー: 7DNZ 8K7C
• EMDBエントリー: 39534
• 分子名称: ATP-binding cassette sub-family B member 6, GLUTATHIONE, CADMIUM ION (3 entities in total)
• 機能のキーワード: cryo-em, abc transporter, atp-binding cassette transporter b6, abcb6, heme biosynthesis, heavy metal detoxification, glutathione, phytochelatin, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 144165.14

構造登録者

Choi, S.H.,Lee, S.S.,Lee, H.Y.,Kim, S.,Kim, J.W.,Jin, M.S. (登録日: 2024-03-20, 公開日: 2024-06-19)

主引用文献

Choi, S.H.,Lee, S.S.,Lee, H.Y.,Kim, S.,Kim, J.W.,Jin, M.S.
Cryo-EM structure of cadmium-bound human ABCB6.
Commun Biol, 7:672-672, 2024

PubMed Abstract: ATP-binding cassette transporter B6 (ABCB6), a protein essential for heme biosynthesis in mitochondria, also functions as a heavy metal efflux pump. Here, we present cryo-electron microscopy structures of human ABCB6 bound to a cadmium Cd(II) ion in the presence of antioxidant thiol peptides glutathione (GSH) and phytochelatin 2 (PC2) at resolutions of 3.2 and 3.1 Å, respectively. The overall folding of the two structures resembles the inward-facing apo state but with less separation between the two halves of the transporter. Two GSH molecules are symmetrically bound to the Cd(II) ion in a bent conformation, with the central cysteine protruding towards the metal. The N-terminal glutamate and C-terminal glycine of GSH do not directly interact with Cd(II) but contribute to neutralizing positive charges of the binding cavity by forming hydrogen bonds and van der Waals interactions with nearby residues. In the presence of PC2, Cd(II) binding to ABCB6 is similar to that observed with GSH, except that two cysteine residues of each PC2 molecule participate in Cd(II) coordination to form a tetrathiolate. Structural comparison of human ABCB6 and its homologous Atm-type transporters indicate that their distinct substrate specificity might be attributed to variations in the capping residues situated at the top of the substrate-binding cavity.

PubMed: 38822018
DOI: 10.1038/s42003-024-06377-1

実験手法

ELECTRON MICROSCOPY (3.2 Å)