Wild Klemens, Bange Gert, Bozkurt Gunes, Segnitz Bernd, Hendricks Astrid, Sinning Irmgard
Heidelberg University Biochemistry Center (BZH), University of Heidelberg, INF328, D-69120 Heidelberg, Germany.
Acta Crystallogr D Biol Crystallogr. 2010 Mar;66(Pt 3):295-303. doi: 10.1107/S0907444910000879. Epub 2010 Feb 12.
The signal recognition particle (SRP) is a conserved ribonucleoprotein (RNP) complex that co-translationally targets membrane and secretory proteins to membranes. The assembly of the particle depends on the proper folding of the SRP RNA, which in mammalia and archaea involves an induced-fit mechanism within helices 6 and 8 in the S domain of SRP. The two helices are juxtaposed and clamped together upon binding of the SRP19 protein to their apices. In the current assembly paradigm, archaeal SRP19 causes the asymmetric loop of helix 8 to bulge out and expose the binding platform for the key player SRP54. Based on a heterologous archaeal SRP19-human SRP RNA structure, mammalian SRP19 was thought not to be able to induce this change, thus explaining the different requirements of SRP19 for SRP54 recruitment. In contrast, the crystal structures of a crenarchaeal and the all-human SRP19-SRP RNA binary complexes presented here show that the asymmetric loop is bulged out in both binary complexes. Differences in SRP assembly between mammalia and archaea are therefore independent of SRP19 and are based on differences in SRP RNA itself. A new SRP-assembly scheme is presented.
信号识别颗粒（SRP）是一种保守的核糖核蛋白（RNP）复合体，它在共翻译过程中将膜蛋白和分泌蛋白靶向运输到膜上。该颗粒的组装依赖于SRP RNA的正确折叠，在哺乳动物和古细菌中，这涉及到SRP S结构域中螺旋6和螺旋8内的诱导契合机制。这两个螺旋并列，在SRP19蛋白与其顶端结合时夹在一起。在当前的组装模式中，古细菌的SRP19会使螺旋8的不对称环向外突出，从而暴露出关键蛋白SRP54的结合平台。基于异源的古细菌SRP19-人类SRP RNA结构，人们认为哺乳动物的SRP19无法诱导这种变化，从而解释了SRP19在招募SRP54时的不同要求。相比之下，本文展示的嗜热栖热菌和全人类的SRP19-SRP RNA二元复合体的晶体结构表明，在这两种二元复合体中，不对称环均向外突出。因此，哺乳动物和古细菌之间SRP组装的差异与SRP19无关，而是基于SRP RNA本身的差异。本文提出了一种新的SRP组装方案。
