A perspective on mechanisms of protein tetramer formation
A perspective on mechanisms of protein tetramer formation
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DOI：
10.1016/s0006-3495(03)74777-8
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发表时间：
2003-12-01
影响因子：
3.4
通讯作者：
Powers, DL
中科院分区：
文献类型：
--
作者：
Powers, ET;Powers, DL
同源四聚体蛋白可以通过几种不同的途径组装，但只观察到使用一条途径，其中两个单体结合形成一个同源二聚体，然后两个同源二聚体结合形成一个同源四聚体。为了确定为什么这一途径应该如此均匀地占优势，我们将可能途径的四聚动力学模拟为每一步的速率常数的函数。我们发现，与其他途径的竞争，可以通过两种不同类型的同源二聚体的结合或通过将单体连续添加到同源二聚体和同源三聚体来形成同源四聚体，可以导致大量的蛋白质作为组装途径的中间体被捕获。我们认为，这可能会导致生物体不受欢迎的后果，选择性压力可能导致同源四聚体蛋白质通过单一途径进化组装。
Homotetrameric proteins can assemble by several different pathways, but have only been observed to use one, in which two monomers associate to form a homodimer, and then two homodimers associate to form a homotetramer. To determine why this pathway should be so uniformly dominant, we have modeled the kinetics of tetramerization for the possible pathways as a function of the rate constants for each step. We have found that competition with the other pathways, in which homotetramers can be formed either by the association of two different types of homodimers or by the successive addition of monomers to homodimers and homotrimers, can cause substantial amounts of protein to be trapped as intermediates of the assembly pathway. We propose that this could lead to undesirable consequences for an organism, and that selective pressure may have caused homotetrameric proteins to evolve to assemble by a single pathway.