CO-OPERATIVITY IN PROTEIN-PROTEIN ASSOCIATION - THE STRUCTURE AND STABILITY OF THE ACTIN FILAMENT
CO-OPERATIVITY IN PROTEIN-PROTEIN ASSOCIATION - THE STRUCTURE AND STABILITY OF THE ACTIN FILAMENT
复制标题
DOI：
10.1016/0022-2836(89)90494-4
复制
发表时间：
1989-04-05
影响因子：
5.6
通讯作者：
ERICKSON, HP
中科院分区：
文献类型：
--
作者：
ERICKSON, HP
蛋白质亚基由两个键同时连接的协同缔合比单独形成任何一个键的缔合要有利得多。本文提出了一个计算协同效应的理论框架，它将广泛应用于蛋白质-蛋白质和蛋白质-DNA缔合。这一理论被详细地应用于行动。肌动蛋白丝的断裂是非常不利的：这里估计退火-断裂的缔合常数至少为1013 M-1。与丝内的这些非常强的键相反，亚基在末端松散地连接，缔合常数为2 × 10 - 4。105 M-1。退火-断裂和末端缔合之间的八个数量级的差异可以归因于退火反应中一个额外的蛋白质-蛋白质键的合作形成。这一观察结果，以及对协同性的定量分析，得出了一个重要的结论：连接长螺距螺旋中的亚基的纵向键必须比连接这些螺旋之间的亚基的对角键强得多。这一结论与最近一些基于傅立叶结构的模型相矛盾，在这些模型中纵向键很弱或不存在。突出的纵向键还需要肌动蛋白丝的刚性，这必须与先前报道的扭转柔性相协调。建议肌动蛋白亚基内的铰链，将其分成两个灵活连接的域。在一种可能的模型中，两个域径向取向：内部域通过纵向和对角键连接以形成相对刚性的螺旋骨架，外部域通过柔性铰链连接到该骨架，允许它们移动10 °的角度。到20度。个或多个.外肌球蛋白结合结构域的灵活性在功能上应该是重要的，允许肌球蛋白跨桥在一系列角度上连接。
Co-operative association, in which a protein subunit is held simultaneously by two bonds, is enormously more favorable than association forming either bond alone. A theoretical framework for calculating the effect of co-operativity is developed here, which should have a broad application to protein-protein and protein-DNA associations. The theory is applied in detail to actin. Fragmentation of an actin filament is extremely unfavorable: the association constant for annealing-fragmentation is estimated here to be at least 1013 M-1. In contrast to these very strong bonds within the filament, subunits are loosely attached at the end, with an association constant of 2 .times. 105 M-1. The eight orders of magnitude difference between annealing-fragmentation and end association can be attributed to the co-operative formation of one additional protein-protein bond in the annealing reaction. This observation, and a quantitative analysis of the co-operativity, lead to an important conclusion: the longitudinal bond, which connects subunits in the long-pitch helix, must be substantially stronger than the diagonal bond, which connect subunits between these helices. This conclusion contradicts some recent models based on Fourier construction, in which the longitudinal bond is weak or absent. Prominent longitudinal bonds also require a rigidity of the actin filament that must be reconciled with previous reports of torsional flexibility. A hinge within the actin subunit is suggested, separating it into two flexibly attached domains. In one possible model the two domains are oriented radially: the inner domains are connected by longitudinal and diagonal bonds to form a relatively rigid helical backbone, and the outer domains are attached to this backbone by flexible hinges, permitting them to move through angles of 10.degree. to 20.degree. or more. Flexibility of the outer myosin-binding domain should be functionally important, permitting attachment of myosin cross-bridges over a range of angles.