5JR8

Disposal of Iron by a Mutant form of Siderocalin NGAL

5JR8 の概要

• エントリーDOI: 10.2210/pdb5jr8/pdb
• 分子名称: Neutrophil gelatinase-associated lipocalin, PHOSPHATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: fe-siderophore binding protein mutant, siderophore binding protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted : P80188
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41144.68

構造登録者

Rupert, P.B.,Strong, R.K.,Barasch, J.,Hollman, M.,Deng, R.,Hod, E.A.,Abergel, R.,Allred, B.,Xu, K.,Darrah, S.,Tekabe, Y.,Perlstein, A.,Bruck, E.,Stauber, J.,Corbin, K.,Buchen, C.,Slavkovich, V.,Graziano, J.,Spitalnik, S.,Qiu, A. (登録日: 2016-05-05, 公開日: 2016-09-28, 最終更新日: 2023-09-27)

主引用文献

Barasch, J.,Hollmen, M.,Deng, R.,Hod, E.A.,Rupert, P.B.,Abergel, R.J.,Allred, B.E.,Xu, K.,Darrah, S.F.,Tekabe, Y.,Perlstein, A.,Wax, R.,Bruck, E.,Stauber, J.,Corbin, K.A.,Buchen, C.,Slavkovich, V.,Graziano, J.,Spitalnik, S.L.,Bao, G.,Strong, R.K.,Qiu, A.
Disposal of iron by a mutant form of lipocalin 2.
Nat Commun, 7:12973-12973, 2016

PubMed Abstract: Iron overload damages many organs. Unfortunately, therapeutic iron chelators also have undesired toxicity and may deliver iron to microbes. Here we show that a mutant form (K3Cys) of endogenous lipocalin 2 (LCN2) is filtered by the kidney but can bypass sites of megalin-dependent recapture, resulting in urinary excretion. Because K3Cys maintains recognition of its cognate ligand, the iron siderophore enterochelin, this protein can capture and transport iron even in the acidic conditions of urine. Mutant LCN2 strips iron from transferrin and citrate, and delivers it into the urine. In addition, it removes iron from iron overloaded mice, including models of acquired (iron-dextran or stored red blood cells) and primary (Hfe) iron overload. In each case, the mutants reduce redox activity typical of non-transferrin-bound iron. In summary, we present a non-toxic strategy for iron chelation and urinary elimination, based on manipulating an endogenous protein:siderophore:iron clearance pathway.

PubMed: 27796299
DOI: 10.1038/ncomms12973

実験手法

X-RAY DIFFRACTION (2.65 Å)