Linked functions in allosteric proteins. Extension of the concerted (MWC) model for ligand-linked subunit assembly and its application to human hemoglobins.
Linked functions in allosteric proteins. Extension of the concerted (MWC) model for ligand-linked subunit assembly and its application to human hemoglobins.
复制标题
变构蛋白中的相关功能。
DOI：
10.1016/0022-2836(81)90400-9
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发表时间：
1981
影响因子：
5.6
通讯作者：
M. L. Johnson
中科院分区：
文献类型：
--
作者：
G. K. Ackers;M. L. Johnson
Monodet等人的变构模型。（1965）（MWC）已经扩展到考虑亚基解离的影响。这个问题是制定理论上的两个变构物种（二聚体和四聚体）连接的聚合反应的一般模型。用变构模型参数解释了二聚体-四聚体缔合常数的关系，并根据最近的实验数据对一般模型的子例进行了检验，这些实验数据是关于正常人血红蛋白和变异血红蛋白堪萨斯（β102，Asp → Thr）中氧合相关的二聚体-四聚体平衡的。这些分析的目的是：（1）找到能够描述两种血红蛋白系统中连接的二聚体-四聚体平衡的最简单模型，以及（2）评估相应的模型参数，以便可以比较两种血红蛋白的变构性质。当α和β链具有相等的结合亲和力时，发现正常血红蛋白和血红蛋白堪萨斯的数据明确排除了该模型。当这个两态模型被修改为允许链的非等价亲和力时，该模型可以拟合血红蛋白堪萨斯，但不能拟合血红蛋白A。一个模型，其中二聚体被允许存在于一个不同于四聚体R状态的状态，被发现与血红蛋白A的数据一致，与α和β链的等效结合。对于血红蛋白A，未配体的R-状态四聚体具有与完全配体的R-状态四聚体不同的亚基解离能。能够描述血红蛋白A和血红蛋白堪萨斯的最简单的模型是通过扩展该三态模型以允许（但不要求）α和β链的功能不等效来获得的。四聚体血红蛋白A和堪萨斯的变构常数近似相等。从血红蛋白A获得的值与先前的估计值相似，而血红蛋白堪萨斯的值比先前估计的值（埃德尔斯坦，1971）低约两个数量级。血红蛋白堪萨斯四聚体的低亲和力并不是因为T-状态物种的异常高的变构常数引起的。这在很大程度上是由于T态β链的氧亲和力大大降低，以及R态和T态亲和力之间的比值降低。
The allosteric model of Monodet al.(1965) (MWC) has been extended to take into account the effects of subunit dissociation. The problem is formulated theoretically in terms of a general model for two allosteric species (dimers and tetramers) linked by a polymerization reaction. Relationships are presented for interpreting the dimer-tetramer association constants in terms of allosteric model parameters.Sub-cases of the general model were tested against recent experimental data on the oxygenation-linked dimer-tetramer equilibria in normal human hemoglobin and in the variant hemoglobin Kansas (β102, Asp → Thr). The objectives of these analyses were: (1) to find the simplest models capable of describing the linked dimer-tetramer equilibria in the two hemoglobin systems, and (2) to evaluate the corresponding model parameters so that allosteric properties of the two hemoglobins may be compared.In the simplest version of the model, the dimer is half of an R-state tetramer. This model was found to be excluded unequivocally by the data for both normal hemoglobin and hemoglobin Kansas when the α and β chains have equal binding affinities. When this two-state model was modified to permit non-equivalent affinities for the chains, the model could be fitted to hemoglobin Kansas, but not to hemoglobin A. A model, in which the dimers are allowed to exist in a state different from the tetramer R state, was found to be consistent with the data for hemoglobin A, with equivalent binding by the α and β chains. For hemoglobin A, the unliganded R-state tetramers have a different subunit dissociation energy from that of fully liganded R-state tetramers. The simplest model capable of describing both hemoglobin A and hemoglobin Kansas was obtained by extending this three-state model to permit (but not require) functional non-equivalence of the α and β chains. For these MWC models, unique estimates were obtained for the model parameters.The allosteric constants for tetrameric hemoglobins A and Kansas are approximately equal. The value obtained from hemoglobin A is similar to previous estimates, whereas the value for hemoglobin Kansas is lower than previously estimated (Edelstein, 1971) by approximately two orders of magnitude. The low affinity of hemoglobin Kansas tetramer does not arise from an unusually high allosteric constant favoring the T-state species. It is largely the consequence of a greatly reduced oxygen affinity of β chains in the T state, and reduced values for the ratio between affinities in the R and T states.