RESUMEN

Sec-pathway is the main protein secretion pathway in prokaryotes and is essential for their survival. The motor protein SecA is the main coordinator of the pathway in bacteria as it is has evolved to perform multiple tasks, acting like a "swiss army knife", from binding pre-proteins to altering its oligomeric and conformational states. This study focuses on the role of its Preprotein Binding Domain (PBD), which is a key protein module that identified in three conformational states (WO, O and C). A thorough analysis was conducted to identify PBD's inter- and intra-protomeric interactions, highlighting the most significant and conserved ones. Both crystallographic and biophysical data indicate that the WO state is the main during dimerization, while the monomeric structure can adopt all three states. C-tail, StemPBD and 3ß-tipPBD are important elements for the stabilization of different oligomeric and conformational states, as they offer specific interactions. Alterations in the lipophilicity of the StemPBD causes increased proteins dynamics or/and Prl phenotype. In the C state, 3ß-tipPBD interacts and opens the ATPase motor. We hypothesize that this partial opening of the motor with the increased dynamics describes the Prl phenotype.