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The extracellular domain of a cell surface receptor (A) was switched with the extracellular domain of another receptor (B) to create a chimeric recept
Question

The extracellular domain of a cell surface receptor (A) was switched with the extracellular domain of another receptor (B) to create a chimeric receptor (B-A). Assuming that there is no effect on the functionality of the domains in the chimeric receptor, what is the most likely outcome in the presence of the ligand for receptor B?

A.

​ The ligand will activate the pathway normally triggered by receptor A.

B.

The ligand will activate the pathway normally triggered by receptor B.

C.

​The chimeric receptor will fail to transduce any signal in response to the ligand.

D.

​The chimeric receptor will cause constitutive activation of the signaling pathway

Correct option is A

In this scenario, the extracellular domain of receptor A has been switched with the extracellular domain of receptor B, creating a chimeric receptor (B-A). The extracellular domain of a receptor is primarily responsible for ligand binding, so if the chimeric receptor is exposed to the ligand for receptor B, it will still have the binding specificity of receptor B. However, the intracellular domain of the chimeric receptor is derived from receptor A, which means that once the ligand binds, the signaling pathway will be the one normally triggered by receptor A. Therefore, the ligand will activate the pathway normally triggered by receptor A.

Information Booster

  1. The extracellular domain of a receptor determines the ligand-binding specificity, while the intracellular domain is responsible for signal transduction.
  2. The chimeric receptor (B-A) will bind the ligand for receptor B but will transduce signals through the intracellular domain of receptor A.
  3. Ligand binding to the extracellular domain of a receptor leads to conformational changes that activate the intracellular signaling machinery.
  4. This type of experiment can be useful for understanding the function of specific intracellular domains and how they contribute to signaling.
  5. The intracellular domain of receptor A in the chimeric receptor (B-A) will activate the signal transduction pathway that is typically activated by receptor A.
  6. The chimeric receptor can still mediate signal transduction, but the pathway activated will be determined by the intracellular domain of receptor A, not by receptor B.

Additional Information

  • Option (b): The ligand will activate the pathway normally triggered by receptor B is incorrect because the intracellular domain of the chimeric receptor is from receptor A, and it will not trigger the signaling pathway normally triggered by receptor B.
  • Option (c): The chimeric receptor will fail to transduce any signal in response to the ligand is incorrect because the chimeric receptor will still transduce a signal, but the signaling pathway will be activated by the intracellular domain of receptor A.
  • Option (d): The chimeric receptor will cause constitutive activation of the signaling pathway is incorrect because there is no mention in the question of a mutation or alteration in the intracellular domain that would lead to constitutive activation. The receptor will function normally upon ligand binding.

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