2LHR

Solution structure of Staphylococcus aureus IsdH linker domain

2LHR の概要

• エントリーDOI: 10.2210/pdb2lhr/pdb
• NMR情報: BMRB: 17862
• 分子名称: Iron-regulated surface determinant protein H (1 entity in total)
• 機能のキーワード: heme acquisition, iron uptake, neat domain, hemoglobin receptor, metal transport
• 由来する生物種: Staphylococcus aureus subsp. aureus
• 細胞内の位置: Secreted, cell wall; Peptidoglycan-anchor (Potential): Q8NW39
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9280.32

構造登録者

Spirig, T.,Clubb, R.T.,Malmirchegini, G.R.,Robson, S.A. (登録日: 2011-08-12, 公開日: 2012-11-14, 最終更新日: 2024-05-15)

主引用文献

Spirig, T.,Malmirchegini, G.R.,Zhang, J.,Robson, S.A.,Sjodt, M.,Liu, M.,Krishna Kumar, K.,Dickson, C.F.,Gell, D.A.,Lei, B.,Loo, J.A.,Clubb, R.T.
Staphylococcus aureus Uses a Novel Multidomain Receptor to Break Apart Human Hemoglobin and Steal Its Heme.
J.Biol.Chem., 288:1065-1078, 2013

PubMed Abstract: Staphylococcus aureus is a leading cause of life-threatening infections in the United States. It requires iron to grow, which must be actively procured from its host to successfully mount an infection. Heme-iron within hemoglobin (Hb) is the most abundant source of iron in the human body and is captured by S. aureus using two closely related receptors, IsdH and IsdB. Here we demonstrate that each receptor captures heme using two conserved near iron transporter (NEAT) domains that function synergistically. NMR studies of the 39-kDa conserved unit from IsdH (IsdH(N2N3), Ala(326)-Asp(660)) reveals that it adopts an elongated dumbbell-shaped structure in which its NEAT domains are properly positioned by a helical linker domain, whose three-dimensional structure is determined here in detail. Electrospray ionization mass spectrometry and heme transfer measurements indicate that IsdH(N2N3) extracts heme from Hb via an ordered process in which the receptor promotes heme release by inducing steric strain that dissociates the Hb tetramer. Other clinically significant Gram-positive pathogens capture Hb using receptors that contain multiple NEAT domains, suggesting that they use a conserved mechanism.

PubMed: 23132864
DOI: 10.1074/jbc.M112.419119

実験手法

SOLUTION NMR