Motor protein function and Microfilament Dynamics The figure below shows a recen

Question

Motor protein function and Microfilament Dynamics

The figure below shows a recently published article about myosin V walking on actin filaments. In panel A it illustrates the mechanics of walking. Panel B shows the changes in chemistry (ATP binding and hydrolysis). Then it puts it all together in panel C for myosin.

a. Which event below causes the affinity of the motor protein for the microfilament to dramatically decrease? (3pts, circle one only)

            a. ADP release

            b. ATP binding

            c. ATP hydrolysis

            d. Pi release

b. Where does the motor protein acquire the ATP to do this cellular work? (3pts)

c. We know that ATP hydrolysis drives the ability of motor proteins to walk on microfilaments. What is the effect of ATP hydrolysis (ATPàADP + Pi) affects the conformation of myosin and its affinity for the microfilament? Hint this is called the recovery stroke! Rubric (4): describe effects ATP hydrolysis on the shape of myosin (2) and its affinity to actin microfilaments (2)

e. Explain the effect of the loss of Pi on the comformation of myosin and its affinity for the microfilament (this is the powerstroke!). Rubric (4): describe effects of Pi release on the shape of myosin (2) and its affinity to actin microfilaments (2)

f. Myosin V walks on actin microfilaments toward their plus ends, but we also know that motor proteins can directly affect to dynamics of the cytoskeletal elements with which they associate. Researchers have found that Myosin V is elevated in metastatic colorectal cancers. Myosin V has been shown to be localized to the leading edge of migrating cells. Hypothesize how Myosin V may affect microfilament dynamics to increase cell migration in cancer cells. Rubric (3): use your understanding of the microfilament dynamics involved in cell motility to postulate on a role for myosin V.

Explanation / Answer

Ans a) Release of Pi.

If you observe the chemical cycle in panel A and the cycle in panel c, the myosin head dissociates from the filament after the release of Pi. The Pi from ATP is utilized for the movement of the the myosin V and once it is utilized, the myosin head is freed from the filament.

Ans b) There are three ways the muscle's motor protein derives energy from.

i) Aerobic respiration - Glycolysis in sarcoplasm (that's just a fancy name for a muscle's cytoplasm), and then the citric acid cycle in the mitochondria. Aerobic respiration is largely responsible for the supply of ATP to the motor proteins.

ii) Anaerobic respiration - This occurs when the body is undergoing strenuous exercise. The heart and the blood can't supply the oxygen required by the muscle cells under these conditions and hence the muscle resorts to anaerobic respiration. Glucose is converted into lactic acid in the muscle. This mode of respiration produces very little ATP

iii) Phosphocreatine. Creatinine consumed through the diet is metabolised as phospho-creatine and stored in the muscle. The phosphate group from Phosphocreatine can bind to ADP that is released after the myosin v filament has moved. Thus it Regenerates ATP, and it is a fast process.

Ans c In this step the binding of ADP-Pi to myosin changes the conformation of the head to be a negative of the microfilament, in other words, it changes in a way to perfectly bind to the microfilament (like two pieces of a jigsaw puzzle). This Increases the affinity of the myosin head for the microfilament

Ans e the release of Pi results in a conformational change that leads to the release of the myosin head while simultaneously propelling it forward. This step indicates that the release of Pi reduces myosin's affinity to the myofilament.

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