Heidelberg University Biochemistry Centre, Heidelberg 69120, Germany.
Heidelberg University Biochemistry Centre, Heidelberg 69120, Germany.
Structure. 2018 Nov 6;26(11):1440-1450.e5. doi: 10.1016/j.str.2018.07.008. Epub 2018 Aug 23.
The Escherichia coli signal recognition particle (SRP) receptor, FtsY, plays a fundamental role in co-translational targeting of membrane proteins via the SRP pathway. Efficient targeting relies on membrane interaction of FtsY and heterodimerization with the SRP protein Ffh, which is driven by detachment of α helix (αN1) in FtsY. Here we show that apart from the heterodimer, FtsY forms a nucleotide-dependent homodimer on the membrane, and upon αN1 removal also in solution. Homodimerization triggers reciprocal stimulation of GTP hydrolysis and occurs in vivo. Biochemical characterization together with integrative modeling suggests that the homodimer employs the same interface as the heterodimer. Structure determination of FtsY NG+1 with GMPPNP shows that a dimerization-induced conformational switch of the γ-phosphate is conserved in Escherichia coli, filling an important gap in SRP GTPase activation. Our findings add to the current understanding of SRP GTPases and may challenge previous studies that did not consider homodimerization of FtsY.
大肠杆菌信号识别颗粒（SRP）受体 FtsY 在通过 SRP 途径进行共翻译靶向膜蛋白方面发挥着重要作用。有效的靶向依赖于 FtsY 与 SRP 蛋白 Ffh 的膜相互作用和异二聚化，这是由 FtsY 中α螺旋（αN1）的脱离驱动的。在这里，我们表明，除了异二聚体外，FtsY 在膜上形成核苷酸依赖性的同源二聚体，并且在 αN1 去除后也在溶液中形成。同源二聚化引发 GTP 水解的相互刺激，并在体内发生。生化特性分析和整合建模表明，同源二聚体使用与异二聚体相同的界面。带有 GMPPNP 的 FtsY NG+1 的结构测定表明，二聚化诱导的γ-磷酸的构象转换在大肠杆菌中是保守的，填补了 SRP GTP 酶激活的一个重要空白。我们的发现增加了对 SRP GTP 酶的现有认识，并且可能挑战以前没有考虑 FtsY 同源二聚化的研究。
