Protein folding is a complex cellular process often assisted by chaperones, but it can also be facilitated by interactions with lipids. Disulfide bond formation is a common mechanism to stabilize a protein. This can help maintain functionality amidst changes in the biochemical milieu, including those relating to energy-transducing membranes. Plastidic Type I Signal Peptidase 1 (Plsp1) is an integral thylakoid membrane signal peptidase which requires an intramolecular disulfide bond for in vitro activity. We have investigated the interplay between disulfide bond formation, lipids, and pH in the folding and activity of Plsp1. By combining biochemical approaches with a genetic complementation assay, we provide evidence that interactions with lipids in the thylakoid membrane have reconstitutive chaperoning activity towards Plsp1. Further, the disulfide bridge appears to prevent an inhibitory conformational change resulting from proton motive force-mimicking pH conditions. Broader implications related to the folding of proteins in energy-transducing membranes are discussed.

蛋白质折叠是一个复杂的细胞过程，通常由分子伴侣协助，但与脂质的相互作用也可以促进蛋白质折叠。二硫键的形成是稳定蛋白质的常见机制。这可以帮助维持生化环境变化中的功能，包括那些与能量转换膜有关的变化。Plastidic I型信号肽酶1（Plsp1）是整体类囊体膜信号肽酶，需要分子内二硫键才能进行体外活性。我们已经研究了二硫键形成，脂质和Plsp1的折叠和活性中的pH之间的相互作用。通过将生物化学方法与遗传互补分析相结合，我们提供了证据，与类囊体膜中的脂质相互作用具有对Plsp1的重组伴侣活性。进一步，二硫键似乎阻止了仿照质子动力的pH条件引起的抑制性构象变化。讨论了与能量转换膜中蛋白质折叠有关的更广泛的含义。