Beernink H T, Morrical S W
Department of Biochemistry, University of Vermont College of Medicine, Burlington 05405, USA.
Biochemistry. 1998 Apr 21;37(16):5673-81. doi: 10.1021/bi9800956.
A prerequisite to genetic recombination in the T4 bacteriophage is the formation of the presynaptic filament-a helical nucleoprotein filament containing stoichiometric amounts of the uvsX recombinase in complex with single-stranded DNA (ssDNA). Once formed, the filament is competent to catalyze homologous pairing and DNA strand exchange reactions. An important component in the formation of the presynaptic filament is the uvsY protein, which is required for optimal uvsX-ssDNA assembly in vitro, and essential for phage recombination in vivo. uvsY enhances uvsX activities by promoting filament formation and stabilizing filaments under conditions of low uvsX, high salt, and/or high gp32 (ssDNA-binding protein) concentrations. The molecular properties of uvsY include noncooperative binding to ssDNA and specific protein-protein interactions with both uvsX and gp32. Evidence suggests that all of these hetero-associations of the uvsY protein are important for presynaptic filament formation. However, there is currently no structural information available on the uvsY protein itself. In this study, we present the first characterization of the self-association of uvsY. Using hydrodynamic methods, we demonstrate that uvsY associates into a stable hexamer (s020,w = 6.0, M = 95 kDa) in solution and that this structure is competent to bind ssDNA. We further demonstrate that uvsY hexamers are capable of reversible association into higher aggregates in a manner dependent on both salt and protein concentration. The implications for presynaptic filament formation are discussed.
T4噬菌体中基因重组的一个先决条件是突触前细丝的形成,这是一种螺旋状核蛋白细丝,含有化学计量的uvsX重组酶与单链DNA(ssDNA)形成的复合物。一旦形成,该细丝就能够催化同源配对和DNA链交换反应。突触前细丝形成中的一个重要成分是uvsY蛋白,它在体外是uvsX-ssDNA组装达到最佳状态所必需的,在体内对噬菌体重组至关重要。uvsY通过促进细丝形成并在低uvsX、高盐和/或高gp32(单链DNA结合蛋白)浓度条件下稳定细丝来增强uvsX活性。uvsY的分子特性包括与ssDNA的非协同结合以及与uvsX和gp32的特异性蛋白质-蛋白质相互作用。有证据表明uvsY蛋白的所有这些异源缔合对于突触前细丝的形成都很重要。然而,目前尚无关于uvsY蛋白本身的结构信息。在本研究中,我们首次对uvsY的自缔合作了表征。使用流体动力学方法,我们证明uvsY在溶液中缔合成稳定的六聚体(s020,w = 6.0,M = 95 kDa),并且这种结构能够结合ssDNA。我们进一步证明uvsY六聚体能够以依赖于盐和蛋白质浓度的方式可逆地缔合成更高的聚集体。文中讨论了其对突触前细丝形成的影响。