The 43 kDa subunit of the chloroplast signal recognition particle, cpSRP43, is an ATP-independent chaperone essential for the biogenesis of the light harvesting chlorophyll-binding proteins (LHCP), the most abundant membrane protein family on earth. cpSRP43 is activated by a stromal factor, cpSRP54, to more effectively capture and solubilize LHCPs. The molecular mechanism underlying this chaperone activation is unclear. Here, a combination of hydrogen–deuterium exchange, electron paramagnetic resonance, and NMR spectroscopy experiments reveal that a disorder-to-order transition of the ankyrin repeat motifs in the substrate binding domain of cpSRP43 drives its activation. An analogous coil-to-helix transition in the bridging helix, which connects the ankyrin repeat motifs to the cpSRP54 binding site in the second chromodomain, mediates long-range allosteric communication of cpSRP43 with its activating binding partner. Our results provide a molecular model to explain how the conformational dynamics of cpSRP43 enables regulation of its chaperone activity and suggest a general mechanism by which ATP-independent chaperones with cooperatively folding domains can be regulated.

叶绿体信号识别颗粒cpSRP43的43 kDa亚基是一种不依赖ATP的分子伴侣，对于光收集的叶绿素结合蛋白（LHCP）（地球上最丰富的膜蛋白家族）的生物发生至关重要。cpSRP43由基质因子cpSRP54激活，以更有效地捕获和溶解LHCP。伴侣激活的分子机制尚不清楚。在这里，氢-氘交换，电子顺磁共振和NMR光谱实验的结合揭示了cpSRP43底物结合域中锚蛋白重复基序的无序转变驱动了它的活化。桥接螺旋中类似的线圈到螺旋过渡，将锚蛋白重复基序连接到第二个色域中的cpSRP54结合位点，介导cpSRP43及其激活结合伴侣的远距离变构通讯。我们的结果提供了一个分子模型来解释cpSRP43的构象动力学如何使它的伴侣活性得以调节，并提出了可以调节具有协作折叠结构域的不依赖ATP的伴侣的一般机制。