You have identified a new drug that inhibits certain forms of cell motility, inc

Question

You have identified a new drug that inhibits certain forms of cell motility, including cell crawling. This drug dramatically decreases the viscosity of gels formed with mixtures of actin and a number of actin-binding proteins. These observations suggest that the drug interferes with the assembly of actin filaments. To determine the mechanism of inhibition involved in actin filament assembly, you take short lengths of actin filaments decorated with myosin heads and mix them with actin monomers in the presence and absence of the drug. You measure the assembly of actin filaments by the determining the viscosity of the solution and examining samples by electron microscopy. A graph showing your results from the viscosity experiment and drawings of the molecules observed by electron microscopy are shown below. The orientation of the filaments is the same in each drawing.

A) How does the drug interfere with actin filament assembly?

B) Why is the rate of actin filament assembly slower in the presence of the drug?

C) Provide an explanation for how the drug inhibits cell motility.

Explanation / Answer

A) This drug is inhibiting binding of actin monomers at the +end and disassembly of monomers at the –end, and thus not allowing the actin filament to grow.

B) This drug is inhibiting the binding of actin monomers at the +end, but delaying the actin disassembly at the – end, so this difference results in the slower assembly.

C) As the drug slows down the actin assembly it inhibits the actin treadmilling, which is the key for cell motility, and thus inhibits the cell motility.

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