蛋白质四聚体形成机制的观点。
A perspective on mechanisms of protein tetramer formation.
作者信息
Powers Evan T, Powers David L
机构信息
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
出版信息
Biophys J. 2003 Dec;85(6):3587-99. doi: 10.1016/S0006-3495(03)74777-8.
Abstract
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.
摘要
同四聚体蛋白可以通过几种不同的途径组装，但据观察仅采用一种途径，即两个单体结合形成一个同二聚体，然后两个同二聚体结合形成一个同四聚体。为了确定为何该途径会如此普遍地占主导地位，我们针对可能的途径，将四聚化动力学建模为各步骤速率常数的函数。我们发现，与其他途径竞争时，即同四聚体可通过两种不同类型同二聚体的结合形成，或者通过单体相继添加到同二聚体和同三聚体上形成，会导致大量蛋白质被困在组装途径的中间体中。我们提出，这可能会给生物体带来不良后果，并且选择压力可能导致同四聚体蛋白进化为通过单一途径进行组装。
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