Question

Family resemblance. Eukaryotic elongation factor 2 is inhibited by ADP ribosylation catalyzed by diphtheria toxin. What other G proteins are sensitive to this mode of inhibition?

Short answer

G proteins like Gs and Gi are sensitive to ADP ribosylation, similar to EF2.

Step-by-step solution

Understanding ADP Ribosylation

ADP ribosylation is a process where an ADP-ribose molecule is transferred to a target protein, modifying and usually inhibiting its function. This modification is catalyzed by specific enzymes, including bacterial toxins like diphtheria toxin.

Identifying Sensitive G Proteins

Many G proteins can be affected by ADP ribosylation, particularly those in the family of G proteins involved in signal transduction. Notably, the adenylate cyclase system's G proteins, including Gs (stimulatory) and Gi (inhibitory), are well known to be sensitive to ADP ribosylation.

Relating to Known Toxins

Cholera toxin and pertussis toxin are examples of bacterial toxins that catalyze ADP ribosylation of Gs and Gi proteins, respectively. These toxins use ADP ribosylation to exert their effects, similar to the diphtheria toxin's effect on eukaryotic elongation factor 2.

Conclusion

Thus, the G proteins that are sensitive to ADP ribosylation include those involved in the adenylate cyclase pathway, such as Gs and Gi proteins, affected by toxins like cholera and pertussis.

Key concepts

G proteins

G proteins, or Guanine nucleotide-binding proteins, are vital molecular switches inside cells. They play a crucial role in transmitting signals from the outside of the cell to the interior. G proteins are called so because they bind guanosine triphosphate (GTP) and guanosine diphosphate (GDP). These proteins are highly versatile and participate in many cellular processes like vision, smell, and neurotransmission.

When G proteins become activated by a receptor on the cell surface, they can influence various signaling pathways. One such pathway involves activating or inhibiting adenylate cyclase, which can affect levels of cyclic AMP, a secondary messenger within cells. The two types of G proteins commonly studied in these pathways are Gs, which stimulates adenylate cyclase, and Gi, which inhibits it.

G proteins' ability to switch between active and inactive states makes them ideal targets for regulation and modification by various factors, including toxins that affect their function through processes like ADP ribosylation.

Diphtheria toxin

Diphtheria toxin, a protein secreted by the bacterium *Corynebacterium diphtheriae*, is a well-known bacterial toxin. It exerts its pathogenic effects by disrupting protein synthesis in host cells. This toxin does so by catalyzing the addition of an ADP-ribose moiety from NAD to the eukaryotic elongation factor 2 (EF-2), effectively halting protein synthesis.

Without functional EF-2, cells can't synthesize new proteins, leading to cellular death and tissue damage, which are characteristic of diphtheria infection. Diphtheria toxin's mechanism is a prime example of how bacterial toxins can manipulate host cell machinery to favor the survival and replication of the bacteria.

Understanding the action of diphtheria toxin not only provides insights into bacterial pathogenesis but also highlights the importance of post-translational modifications like ADP ribosylation in regulating protein function.

Signal transduction

Signal transduction is the process by which cells respond to external signals, a vital aspect of cellular communication. Signals can come from hormones, neurotransmitters, growth factors, or other molecules.

The signal transduction process involves the conversion of an extracellular signal into an intracellular response. G proteins are key players in this process, acting as intermediaries that relay the signal from surface receptors to target enzymes or ion channels inside the cell. For instance, when a hormone binds to a receptor, it may activate a G protein, which in turn activates or inhibits adenylate cyclase.

This leads to changes in the concentration of second messengers like cyclic AMP, ultimately triggering specific cellular responses such as gene expression, cell division, or metabolic changes. Signal transduction is crucial for maintaining homeostasis and normal cellular functions.

Bacterial toxins

Bacterial toxins are potent biochemical substances produced and secreted by bacteria, capable of causing harm to their hosts by attacking specific cellular components. These toxins come in various forms and serve diverse functions, often aiding bacteria in colonization, evading the immune system, or extracting nutrients from host tissues.

Some of the well-known bacterial toxins include the diphtheria toxin, cholera toxin, and pertussis toxin. All these toxins utilize ADP ribosylation to interfere with cellular functions. For instance, cholera toxin targets the Gs protein, leading to overstimulation of adenylate cyclase and excessive secretion of water and electrolytes into the gut, resulting in diarrhea.

Pertussis toxin, on the other hand, targets Gi proteins, causing the opposite effect by preventing the normal inhibition of adenylate cyclase. Understanding bacterial toxins' mechanisms is essential for developing methods to prevent and treat bacterial infections effectively.