When reading through the works of those who study the SRP pathway, it becomes clear that these scientists have tremendous respect for the subject of their research. There are no complaints about the system being jury-rigged, a hodgepodge, or messy. On the contrary, as we have come to better understand how this system works, the researchers are under the impression that it is a very sophisticated system. It has been independently described as an “elegant pathway,” [24] an “elegant mechanism,” [25] and “a very elegant solution” [26]. We can likewise get a feel for the way scientists greatly respect the sophistication of this system by considering some excerpts from their studies. One team of researchers notes that “structural studies suggest that the relative position of the N and GTPase domains change during the targeting cycle in response to external cues and serves as an important indicator of the status of the protein” [13]. They also observe ”it appears that two half-reactions (binding of the signal peptide and assembly or activation of the translocon) must be monitored independently and then brought together before a translocation event can be initiated.” Another team notes, “targeting involves a series of ordered steps in which cargo binding and release must occur at the proper stages. Each of the conformational changes in the GTPase domains of the SRP and SR described above provides a potential point at which such control can be exerted, thereby coordinating the loading and unloading of cargoes” [27]. A team of reviewers comments that an “intrinsic advantage of cotranslational protein targeting is that the coupling of translation and translocation should prevent misfolding of the nascent chain in the cytoplasm” [9]. And yet another set of SRP researchers comment on the way the M domain interacts with the NG domain after binding of the signal sequence, observing that this “would elegantly link signal sequence binding to the M domain with GTP binding to the G protein” [10]. The same researchers also describe the central role of the particle protein (SRP54): “SRP function relies on the tightly controlled communication of SRP54 with the external regulators (e.g., the ribosome, the SR, and the translocon) and on internal communication between the domains of SRP54.” Since “the efficiency and fidelity of the targeting process are crucial for maintaining the remarkable organization that is essential for life” [16], it is not surprising that such an elegant and logical system would have been put into place to carry out the task.
Continue reading →