Not All SecA Proteins Are Created Equal: A Study of the SecA1 and SecA2 Proteins of Mycobacterium tuberculosis.
Date of Completion
SecA, tuberculosis, fluorescence, ATPase, nucleotide, secretion
Carolyn M. Teschke
Field of Study
Doctor of Philosophy
In bacteria, most secreted proteins are exported through the SecYEG translocon by the SecA ATPase motor via the general Sec pathway. The identification of an additional SecA protein, particularly in Gram-positive pathogens, has raised important questions about the role of SecA2 both in protein export and establishment of virulence. In Mycobacterium tuberculosis, the causative agent of Tuberculosis (TB), the accessory SecA2 protein possesses ATPase activity that is required for bacterial survival in host macrophages, highlighting its importance in virulence. This study probes the biochemical differences between the two SecA proteins in order to gain insight into how they interact with the same translocon to exporting specific precursors. The study shows that SecA2 unlike SecA1 does not associate with the membrane under normal conditions. SecA2 also binds ADP with much higher affinity than SecA1 and releases the nucleotide more slowly. Nucleotide binding regulates movement of the precursor-binding domain in SecA2, unlike in SecA1 or conventional SecA proteins. This conformational change involving closure of the clamp in SecA2 may provide a mechanism for the cell to direct protein export through the conventional SecA1 pathway under normal growth conditions while preventing ordinary precursor proteins from interacting with the specialized SecA2 ATPase.
D'Lima, Nadia G., "Not All SecA Proteins Are Created Equal: A Study of the SecA1 and SecA2 Proteins of Mycobacterium tuberculosis." (2014). Doctoral Dissertations. 366.