Oxygen dissociation from ferrous oxygenated human hemoglobin:haptoglobin complexes confirms that in the R-state α and β chains are functionally heterogeneous
Oxygen dissociation from ferrous oxygenated human hemoglobin:haptoglobin complexes confirms that in the R-state α and β chains are functionally heterogeneous
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DOI：
10.1038/s41598-019-43190-x
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发表时间：
2019-05-01
影响因子：
4.6
通讯作者：
Coletta, Massimiliano
中科院分区：
文献类型：
--
作者：
Ascenzi, Paolo;Polticelli, Fabio;Coletta, Massimiliano
红细胞外血红蛋白（Hb）的不利影响被几种血浆蛋白抵消，这些蛋白致力于促进游离血红素和Hb的清除。特别地，触珠蛋白（Hp）捕获Hb的α β二聚体，其通过CD 163受体介导的内吞作用递送至网状内皮系统。由于Hp：Hb复合物显示基于血红素的反应性，因此已经确定了O-2从亚铁氧化的人Hp 1 -1：Hb和Hp 2 -2：Hb复合物（分别为Hp 1 -1：Hb（11）-O-2和Hp 22：H B（II）-O-2）解离的动力学。O-2从Hp 1 -1：Hb（11）-O-2和Hp 22：Hb（III）-O-2的解离遵循双相过程。快相和慢相的相对幅度范围在总幅度的0.47和0.53之间，值为k（off 1），（范围在25.6 +/- 1.4 s（-1）和29.1 +/- 1.3 s（-1）之间），比k（off 2）快两倍左右（范围在13.8 +/- 1.6 s（-1）和16.1 +/- 1.2 s（-1）之间）。k（off 1）和k（off 2）的值基本上相同，与在加入连二亚硫酸盐溶液之后或在连二亚硫酸盐存在下用CO溶液置换O-2之后是否进行O-2解离无关。它们对应于那些报告的解离的第一个O-2分子从四聚体血红蛋白（II）-O-2，表明在R-状态的α和β链是功能异质性和四聚体和二聚体的行为相同。因此，与Hp结合的Hb二聚体的α和β链的结构构象对应于R-状态的Hb四聚体的亚基的结构构象。
The adverse effects of extra-erythrocytic hemoglobin (Hb) are counterbalanced by several plasma proteins devoted to facilitate the clearance of free heme and Hb. In particular, haptoglobin (Hp) traps the alpha beta dimers of Hb, which are delivered to the reticulo-endothelial system by CD163 receptormediated endocytosis. Since Hp:Hb complexes show heme-based reactivity, kinetics of O-2 dissociation from the ferrous oxygenated human Hp1-1:Hb and Hp2-2:Hb complexes (Hp1-1:Hb(11)-O-2 and Hp22:H b(II)-O-2, respectively) have been determined. O-2 dissociation from Hp1-1:Hb(11)-O-2 and Hp22:Hb(III)-O-2 follows a biphasic process. The relative amplitude of the fast and slow phases ranges between 0.47 and 0.53 of the total amplitude, with values of k(off1), (ranging between 25.6 +/- 1.4 s(-1) and 29.1 +/- 1.3 s(-1)) being about twice faster than those of k(off2) (ranging between 13.8 +/- 1.6 s(-1) and 16.1 +/- 1.2 s(-1)). Values of k(off1) and k(off2) are essentially the same independently on whether O-2 dissociation has been followed after addition of a dithionite solution or after O-2 displacement by a CO solution in the presence of dithionite. They correspond to those reported for the dissociation of the first O-2 molecule from tetrameric Hb(II)-O-2, indicating that in the R-state alpha and beta chains are functionally heterogeneous and the tetramer and the dimer behave identically. Accordingly, the structural conformation of the alpha and beta chains of the Hb dimer bound to Hp corresponds to that of the subunits of the Hb tetramer in the R-state.