Question

15. You are examining the effects of mutations on a nuclear pore. For the following cases below, describe 1. where in the process of nuclear import function will stop 2. what is being affected and 3. if function can still occur and WHY:

a. The nuclear localization signal is mutated on a nuclear protein.

b. The nuclear transport receptor cannot bind to the nuclear protein.

c. A limited amount of GAP is available in the cell to hydrolyze the GTP.

d. Nuclear transport proteins pass through with nuclear proteins but cannot be recycled to the cytosolic side of the cell.

e. The nuclear protein is unable to unfold.

Answer 1

• NLS sequences are short sequences of about 6 to 8 amino acids, with arginine and lysine amino acids (basic or positive charged). These sequences can associate with nuclear transport receptors (TRs) and helps in transport of cytosolic protein through nuclear membrane pores.
• Muation in signal sequence will prevent the passage through nuclear pores.
• Similarly non-functional receptor or receptor binding may also interrupt passage though nuclear pores.
• Nuclear transport is also controlled by GTPases belonging to RAS superfamily.
• GTP binding causes a “switch on” of certain proteins in the alpha subunit by conformational changes of the alpha helices (that prevents the hydrolysis) of GTP in inactive state), like switch I and switch II.
• This mediates the GTPase activity and GTP hydrolysis.
• GAPs are GTP-activating proteins that increase GTP hydrolysis and act as antagonists for GTPases.

Thus, mutations causing limited GAP will not effect the process.

Answer: c