7W79

Heme exporter HrtBA in complex with Mn-AMPPNP

7W79 の概要

• エントリーDOI: 10.2210/pdb7w79/pdb
• 分子名称: Putative ABC transport system, ATP-binding protein, Putative ABC transport system integral membrane protein, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: heme efflux, heme extraction, heme detoxification, abc transporter, 4-helix tmd, membrane protein
• 由来する生物種: Corynebacterium diphtheriae NCTC 13129; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60214.92

構造登録者

Hisano, T.,Nakamura, H.,Rahman, M.M.,Tosha, T.,Shirouzu, M.,Shiro, Y. (登録日: 2021-12-04, 公開日: 2022-06-22, 最終更新日: 2024-05-29)

主引用文献

Nakamura, H.,Hisano, T.,Rahman, M.M.,Tosha, T.,Shirouzu, M.,Shiro, Y.
Structural basis for heme detoxification by an ATP-binding cassette-type efflux pump in gram-positive pathogenic bacteria.
Proc.Natl.Acad.Sci.USA, 119:e2123385119-e2123385119, 2022

PubMed Abstract: Bacterial pathogens acquire heme from the host hemoglobin as an iron nutrient for their virulence and proliferation in blood. Concurrently, they encounter cytotoxic-free heme that escapes the heme-acquisition process. To overcome this toxicity, many gram-positive bacteria employ an ATP-binding cassette heme-dedicated efflux pump, HrtBA in the cytoplasmic membranes. Although genetic analyses have suggested that HrtBA expels heme from the bacterial membranes, the molecular mechanism of heme efflux remains elusive due to the lack of protein studies. Here, we show the biochemical properties and crystal structures of HrtBA, alone and in complex with heme or an ATP analog, and we reveal how HrtBA extracts heme from the membrane and releases it. HrtBA consists of two cytoplasmic HrtA ATPase subunits and two transmembrane HrtB permease subunits. A heme-binding site is formed in the HrtB dimer and is laterally accessible to heme in the outer leaflet of the membrane. The heme-binding site captures heme from the membrane using a glutamate residue of either subunit as an axial ligand and sequesters the heme within the rearranged transmembrane helix bundle. By ATP-driven HrtA dimerization, the heme-binding site is squeezed to extrude the bound heme. The mechanism sheds light on the detoxification of membrane-bound heme in this bacterium.

PubMed: 35767641
DOI: 10.1073/pnas.2123385119

実験手法

X-RAY DIFFRACTION (3.1 Å)