Structural and mechanistic basis for the regulation of the chloroplast signal recognition particle by (p)ppGpp.

Abstract

The alarmones (p)ppGpp play a critical role in chloroplasts by acting as signalling molecules that regulate gene expression, protein synthesis and chloroplast (cp) development, particularly in response to stress and nutrient availability. However, the underlying molecular mechanisms are still poorly understood. Here, we show that (p)ppGpp binds to the GTPase-containing NG domains of the chloroplast signal recognition particle (SRP) and its receptor, preventing their GTP-dependent association through a competitive mechanism. The structure of (cp)FtsY bound to ppGpp reveals that the alarmone employs the same binding mode as its GDP counterpart and hinders chloroplast SRP:FtsY complex formation via its pyrophosphate moiety. Consequently, (p)ppGpp also inhibits the mutual stimulation of the two GTPases present in the (cp)SRP54:FtsY complex. Taken together, our findings provide the first description of how the alarmones (p)ppGpp may regulate the SRP-dependent protein trafficking pathway in plants.