title: ADP-dependent conformational changes distinguish Mycobacterium tuberculosis SecA2 from SecA1.
abstract: In bacteria, most secreted proteins are exported through the SecYEG translocon by the SecA ATPase motor via the general secretion or "Sec" pathway. The identification of an additional SecA protein, particularly in Gram-positive pathogens, has raised important questions about the role of SecA2 in both protein export and establishment of virulence. We previously showed in Mycobacterium tuberculosis, the causative agent of tuberculosis, the accessory SecA2 protein possesses ATPase activity that is required for bacterial survival in host macrophages, highlighting its importance in virulence. Here, we show that SecA2 binds ADP with much higher affinity than SecA1 and releases the nucleotide more slowly. Nucleotide binding also 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.
authors.affiliation: From the Departments of Molecular and Cell Biology and.
authors.forename: Nadia G
authors.initials: NG
authors.lastname: D'Lima
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Teschke
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D000244:Adenosine Diphosphate; D000251:Adenosine Triphosphatases; C442122:SecA1 protein, Mycobacterium tuberculosis; C442123:SecA2 protein, Mycobacterium
keywords: ATPases; FRET; Protein Export; Secretion; Tuberculosis