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

ID: 64485 • Letter: Y

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.

No drug Plus end Minus end no drug 3.0 2.0 drug +drug 1.0 0.0 10 Time (min) O Actin monomer Myosin head

Explanation / Answer

A)

Actin is a round protein. The molecules of actin bind together in a long chain to form filament. The actin filaments are semi-flexible polymers and are built from dimer pair of actin monomers.

The two monomers assemble to form the actin filaments based on the polarity of monomers. The drug interferes with the polarity of monomers.

B)

The change in polarity caused by the drug results in decreased rate of assembly of the actin filaments.

C)

During muscle contraction, the movement of myosin head causes thin filaments to move. The thin filaments are attached to a protein plate called Z-disc. The drug prevents the anchoring of thin filaments to Z-disc. Thus, the thick filaments simply slide over thin filaments in opposite direction without causing the movement. Thus, the drug can inhibit the cell motility until its saturation with existing monomers.

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