Structural investigations into the interaction of hemoglobin and part structures with bacterial endotoxins
Structural investigations into the interaction of hemoglobin and part structures with bacterial endotoxins
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DOI：
10.1177/1753425907087257
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发表时间：
2008-02-01
期刊：
影响因子：
3.2
通讯作者：
Brandenburg, Klaus
中科院分区：
文献类型：
--
作者：
Howe, Joerg;Garidel, Patrick;Brandenburg, Klaus
细菌内毒素（脂多糖，LPS）与氧转运蛋白血红蛋白的相互作用机制的细节的理解仍然缺乏，尽管其高度的生物相关性。在这里，生物物理调查内毒素：血红蛋白的相互作用，其中包括使用各种粗糙的突变体LPS以及游离脂质A;除了完整的血红蛋白分子从胎羊提取物，还研究了部分结构α链和血红素免费的样品。调查包括脂多糖的酰基链的凝胶-液晶相行为的测定，内毒素的超微结构（聚集体结构和形态的类型），以及血红蛋白掺入人工免疫细胞膜和LPS。我们的数据表明，血红蛋白和LPS之间的相互作用的模型，其中血红蛋白不强烈反应的亲水性或与LPS的疏水性部分，但与完整的内毒素聚集体。Hb能够以平行于脂A双层的纵向掺入LPS中。虽然这不会导致LPS酰基链堆积的强烈干扰，但曲率的变化导致略微圆锥形的分子形状，其三维排列从单层变为立方LPS聚集体。我们以前的研究结果表明，立方结构的LPS具有很强的内毒素活性。本文所述的Hb对LPS物理状态的性质可以解释由于Hb的作用而观察到的LPS介导的内毒性增加。
An understanding of details of the interaction mechanisms of bacterial endotoxins (lipopolysaccharide, LPS) with the oxygen transport protein hemoglobin is still lacking, despite its high biological relevance. Here, a biophysical investigation into the endotoxin:hemoglobin interaction is presented which comprises the use of various rough mutant LPS as well as free lipid A; in addition to the complete hemoglobin molecule from fetal sheep extract, also the partial structure alpha-chain and the heme-free sample are studied. The investigations comprise the determination of the gel-to-liquid crystalline phase behaviour of the acyl chains of LPS, the ultrastructure (type of aggregate structure and morphology) of the endotoxins, and the incorporation of the hemoglobins into artificial immune cell membranes and into LPS. Our data suggest a model for the interaction between Hb and LPS in which hemoglobins do not react strongly with the hydrophilic or with the hydrophobic moiety of LPS, but with the complete endotoxin aggregate. Hb is able to incorporate into LPS with the longitudinal direction parallel to the lipid A double-layer. Although this does not lead to a strong disturbance of the LPS acyl chain packing, the change of the curvature leads to a slightly conical molecular shape with a change of the three-dimensional arrangement from unilamellar into cubic LPS aggregates. Our previous results show that cubic LPS structures exhibit strong endotoxic activity. The property of Hb on the physical state of LPS described here may explain the observation of an increase in LPS-mediating endotoxicity due to the action of Hb.