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6 Dec 2018

2. Let’s consider transport of iodine (I- ) into your thyroid cells. You need iodine in your diet for normal thyroid activity, but dietary iodine concentrations are very low (usually in America we get enough just from what is added to iodized salt). People have been interested for some time in trying to figure out how we can transport iodine so efficiently. One way we can study the transporter is to look for mutations that alter its function, and therefore lead to thyroid problems.

A. The transporter is a rocker-switch type Na+ / Isymport. The pivot of the rocker mechanism is a glycine amino acid, #93 in the primary structure of the transporter. Some people with thyroid problems have a mutation that changes this glycine to an arginine. Define what is meant by “the primary structure” of the transporter. Explain how that change would alter the function of the transporter. (You may consult the structure of arginine on slide 7 of Lecture 3.)

B. There is normally an Arginine at position #124 in the primary structure of the transporter. This Arginine participates in hydrogen bonding with an Asparagine, positioned at #441 in the primary structure. There is evidence that these H-bonds are present in the outward-facing transporter conformation, but are broken when the transporter switches to the inward-facing conformation. People with mutations that replace Arginine 124 with Histidine have difficulty transporting Iodine into their thyroid cells. Copy the structures of Arginine and Asparagine. Label relevant H-bond donor and acceptor atoms between these two amino acids. Explain how replacing Arginine 124 with Histidine could affect the operation of the transporter. (Make a sketch of the transporter in the inward-facing and outward-facing conformations to help you to visualize this.)

C. Recent investigation demonstrated that there are actually TWO Na+ ions symported with the Iion. When a colleague of mine saw this report, he said “Ah ha! So that’s why iodine transport is so efficient!” Explain why it would make a difference whether one or two sodium ions were involved? Why would involving two sodium ions make the transporter more efficient?

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Nestor Rutherford
Nestor RutherfordLv2
8 Dec 2018

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