A pharmaceutical researcher is studying a target protein involved in the signal transduction and cellular response to TSH. The protein is isolated and purified from thyroid follicular cells. Further analysis reveals that the protein contains multiple alpha-helical regions. Each of these regions is composed of approximately 20 amino acid residues consisting primarily of valine, alanine, and isoleucine. This particular region of the protein most likely performs which of the following functions?

Question

A pharmaceutical researcher is studying a target protein involved in the signal transduction and cellular response to TSH.  The protein is isolated and purified from thyroid follicular cells.  Further analysis reveals that the protein contains multiple alpha-helical regions.  Each of these regions is composed of approximately 20 amino acid residues consisting primarily of valine, alanine, and isoleucine.  This particular region of the protein most likely performs which of the following functions?

Quizplus · Accepted Answer

11ec160b_36b9_08e0_9249_b7178793fcbc_MD0001_00 G protein-coupled receptors that bind glycoprotein hormones (eg, TSH, LH, FSH) contain 3 major domains: an extracellular domain responsible for ligand binding, a transmembrane domain, and an intracellular domain coupled with heterotrimeric G proteins. The transmembrane domain is made up of nonpolar, hydrophobic amino acids (eg, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline, glycine). These amino acids are arranged in an alpha-helical fashion and project their hydrophobic R groups outwardly, anchoring the transmembrane region of the protein to the hydrophobic core of the phospholipid bilayer. The transmembrane domain may also play an important role in cellular signaling and transport. (Choice B) Binding of a ligand to the extracellular domain of a transmembrane receptor can result in activation of the cAMP or phosphatidylinositol second messenger system, activation of receptor tyrosine kinases, opening of ion channels, and activation of the calcium-calmodulin system. The extracellular domain of these receptors is typically composed of hydrophilic amino acids. (Choice C) Activation of G protein-coupled receptors utilizing the cAMP second messenger system results in increased synthesis of intracellular cAMP and subsequent activation of protein kinase A. Protein kinase A then phosphorylates cytosolic proteins that translocate into the nucleus and bind to DNA promoter regions to modulate transcription. (Choice D) Intracellular iron-containing proteins (hemeproteins) include hemoglobin, myoglobin, and cytochrome oxidase. Heme is a complex of protoporphyrin IX and iron. Hemoglobin A, the most common hemoglobin in adults, consists of 2 alpha and 2 beta globin chains held together by noncovalent interactions. Each subunit contains stretches of alpha helices that form a heme-binding pocket lined by nonpolar amino acids. (Choice E) Insulin and IGF-1 bind to receptors that possess tyrosine kinase on their intracellular domain (receptor tyrosine kinases). These receptors dimerize upon ligand binding to the extracellular domain, which subsequently activates tyrosine kinase. Tyrosine kinase phosphorylates tyrosine residues, triggering a downstream cellular response. Educational objective: Integral membrane proteins contain transmembrane domains composed of alpha helices with hydrophobic amino acid residues (eg, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline, glycine). These transmembrane domains help anchor the protein to the phospholipid bilayer of the cell membrane. __________ References: G protein coupled receptor structure and activation. (http://www.ncbi.nlm.nih.gov/pubmed/17188232) Transmembrane domains participate in functions of integral membrane proteins. (http://www.ncbi.nlm.nih.gov/pubmed/8744829)

A Pharmaceutical Researcher Is Studying a Target Protein Involved in the Signal