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Photorhabdus asymbiotica (Pa..shown below) is a naturally bioluminescent bacteri

ID: 59064 • Letter: P

Question

Photorhabdus asymbiotica (Pa..shown below) is a naturally bioluminescent bacterium that normally infects soil nematodes. However, Pa is an emerging human pathogen that causes skin and soft tissue lesions in farm workers exposed to nematode-infested soil. The toxin (PaTox) responsible for this covalently modifies different G proteins. In this case, PaTox glycosylates a tyrosine on Rho. This causes the MF cytoskeleton to collapse and prevents cell migration in response to extracellular growth factors. Thus, skin abrasions in infected individuals heal very slowly. Based on this information, how does PaTox affect Rho function?

A. PaTox causes Rho to constitutively bind formin.

B. PaTox causes Rho to constitutively bind WAVE or WASp.

C. PaTox prevents Rho from activating profilin.

D. PaTox prevents Rho from exchanging GDP for GTP.

E. PaTox prevents Rho from hydrolyzing GTP.

Explanation / Answer

E. PaTox prevents Rho from hydrolyzing GTP.

Rho proteins are small GTPases and important regulators of cellular signal transduction. GTPases can change from their active GTP-bound into their inactive GDP-bound forms by hydrolysis of GTP. GTP-bound Rho can activate further effectors, e.g. the Rho kinase enzyme that regulates the cells’ actin cytoskeleton.

The PaTox toxin interferes with the hydrolysis of Rho-GTP into inactive Rho-GDP. PaTox does this by attaching a sugar residue (N-acetylglucosamine) to Rho, thereby setting the entire switch to “off”. The protein can no longer activate effectors and cannot be activated itself either.