Bacteriophage holins: deadly diversity.
Bacteriophage holins: deadly diversity.
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发表时间：
2002
影响因子：
1.2
通讯作者：
R. Young
中科院分区：
文献类型：
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作者：
R. Young
噬菌体生物学是分子遗传学许多基本范式的来源。l、T4和T7等噬菌体的感染周期已被详细描述；基因表达的精确序列和许多决定性的调控事件是已知的。事实上，生物学中唯一被充分理解并能在分子水平上定量建模的发育步骤是噬菌体1中溶解途径和溶原途径之间的选择（McAdams和Shapiro， 1995）。然而，感染周期的终止事件——宿主细胞的裂解——通常被视为噬菌体编码的杀伤活性积累的微不足道和不可避免的结果（Watson等人，1987）。直到最近，人们才意识到，宿主裂解事件也是被精心编程的。事实上，在营养循环中唯一关键的调控决定是何时对宿主进行裂解。决定这一事件发生时间并为裂解提供必要功能的分子是保持蛋白（Wang et al., 2000）。Holins是一种小的膜蛋白，作为一种功能基团，被定义不到十年（Young, 1992）。尽管近年来在定义holin介导现象的范围方面取得了相当大的进展，但必须从一开始就强调，我们对这些构成自然界中最多样化的功能同源物的显著蛋白质的研究在很大程度上仍处于描述阶段（Wang et al., 2000）。对于holin在结构层面上的作用以及它们在机制层面上的作用我们所知甚少。事实上，holins在溶解过程中引起的致死性病变的性质尚不清楚；它是膜上一个确定的孔，一个随机尺寸的稳定孔的集合，还是一个不稳定的动态孔，反映了holins之间松散的分子间相互作用，还是由高度低聚的holins簇引起的不规则变形？尽管如此，holins已经被揭示为解决生物时序问题的优雅简单的解决方案，因此它们必须吸引越来越多的关注和研究，即使它们的膜定位和致死性表型对生化研究构成了艰巨的障碍。
Bacteriophage biology has been the source of many of the fundamental paradigms of molecular genetics. The infective cycles of phages like l, T4, and T7 have been characterized in great detail; the precise sequence of gene expression and many of the decisive regulatory events are known. Indeed, the only developmental step in biology that is sufficiently well understood to be quantitatively modelled at the molecular level is the choice between the lytic and lysogenic pathways in phage l (McAdams and Shapiro, 1995). However, the terminating event of the infective cycle – lysis of the host cell – was generally viewed as the trivial and inevitable outcome of the accumulation of phage-encoded muralytic activity (Watson et al., 1987). It is only recently that it has become appreciated that the host lysis event is also exquisitely programmed. It will be argued here that, in fact, the only critical regulatory decision in the vegetative cycle is when to effect lysis of the host. The molecule which determines the timing of this event and also provides function essential to lysis is the holin (Wang et al., 2000). Holins are small membrane proteins that, as a functional group, have been defined for less than a decade (Young, 1992). Although considerable progress has been made in recent years in defining the scope of holin-mediated phenomena, it must be emphasized from the outset that we are still largely in the descriptive phase of the study of these remarkable proteins which constitute the most diverse group of functional homologs in nature (Wang et al., 2000). There is very little known about holins at the structural level or about how they function at the mechanistic level. In fact, the nature of the lethal lesion caused by holins in the process of lysis is still unknown; is it a defined pore in the membrane, a collection of stable pores of random dimensions, or an unstable, dynamic pore reflecting loose intermolecular interactions between holins, or irregular deformities caused by highly oligomeric clusters of holins? Nevertheless, holins have been revealed as such elegantly simple solutions to the problem of biological timing that they must attract increasing attention and study, even though their membrane localization and lethal phenotype pose daunting obstacles to biochemical investigation.