Peptides selected for the protein nanocage pores change the rate of iron recovery from the ferritin mineral
Peptides selected for the protein nanocage pores change the rate of iron recovery from the ferritin mineral
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DOI：
10.1074/jbc.c700153200
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发表时间：
2007-11-02
影响因子：
4.8
通讯作者：
Theil, Elizabeth C.
中科院分区：
文献类型：
--
作者：
Liu, Xiaofeng S.;Patterson, Leslie D.;Theil, Elizabeth C.
孔隙调节铁蛋白纳米笼内部的含铁生物矿物与铁蛋白纳米笼外部的还原剂/螯合剂之间的通道，以控制铁的脱矿率。通过晶体学、铁去除率和CD光谱观察到，由三个亚基组成的孔螺旋/环/螺旋基序独立于蛋白笼展开。在野生型铁蛋白中，升高的温度或尿素（1- 10mm）、生理尿素范围、0.1 mM胍或保守的孔氨基酸突变都能诱导孔展开。从组合七肽库中选择用于铁蛋白孔结合的肽，将铁脱矿率提高了3倍（p < 0.001），类似于打开孔的突变。将多肽偶联到治疗用螯合剂去铁胺B甲磺酸(R)，使发生率增加到8倍（p < 0.001）。第二孔结合肽具有相反的作用，使铁脱矿率降低60% （p < 0.001）。这些肽可能具有药理作用，并可能模拟体内铁蛋白脱矿率的调节剂或膜门控孔的肽调节剂。结果表明，小肽可以利用蛋白质孔的结构可塑性来调节功能。
Pores regulate access between ferric-oxy biomineral inside and reductants/chelators outside the ferritin protein nanocage to control iron demineralization rates. The pore helix/loop/helix motifs that are contributed by three subunits unfold independently of the protein cage, as observed by crystallography, Fe removal rates, and CD spectroscopy. Pore unfolding is induced in wild type ferritin by increased temperature or urea (1-10 mM), a physiological urea range, 0.1 mM guanidine, or mutation of conserved pore amino acids. A peptide selected for ferritin pore binding from a combinatorial, heptapeptide library increased the rate of Fe demineralization 3-fold (p < 0.001), similarly to a mutation that unfolded the pores. Conjugating the peptide to Desferal (R) (desferrioxamine B mesylate), a chelator in therapeutic use, increased the rates to 8-fold (p < 0.001). A second pore binding peptide had the opposite effect and decreased the rate of Fe demineralization 60% (p < 0.001). The peptides could have pharmacological uses and may model regulators of ferritin demineralization rates in vivo or peptide regulators of gated pores in membranes. The results emphasize that small peptides can exploit the structural plasticity of protein pores to modulate function.