<h2 data-type="title">Protein Structure</h2>
<p>Recall that the shape of a protein is critical to its function. For example, an enzyme can bind to a specific substrate at a site we refer to as the active site. If local changes or changes in overall protein structure alter this active site, the enzyme may be unable to bind to the substrate.</p>
<p>In order to understand how the protein gets its final shape or conformation, we need to understand the four levels of protein structure. Generally, these levels are <strong>primary</strong>, <strong>secondary</strong>, <strong>tertiary</strong>, and <strong>quaternary</strong>.</p>
<h2 data-type="title">Primary Structure</h2>
<p id="fs-id1277293">The unique sequence of amino acids in a polypeptide chain is its <span data-type="term">primary structure</span>. For example, the pancreatic hormone insulin has two polypeptide chains, A and B. These chains are linked together by disulfide bonds. The N terminal amino acid of the A chain is glycine. On the other hand, the C terminal amino acid is asparagine (<a href="#attachment_95339">see image below</a>). The sequences of amino acids in the A and B chains are unique to insulin.</p>
<div class="wp-caption alignnone" id="attachment_95339" style="width: 1000px"><a href="https://data.ulearngo.com/assets/3c258a74-e8a7-4af4-ae14-b1d08aa230ed"><img alt="insulin-protein" class="size-full wp-image-95339" height="489" src="https://data.ulearngo.com/assets/3c258a74-e8a7-4af4-ae14-b1d08aa230ed" width="1000"/></a><p class="wp-caption-text">Bovine serum insulin is a protein hormone made of two peptide chains. The chains are A (21 amino acids long) and B (30 amino acids long). In each chain, primary structure is indicated by three-letter abbreviations. Basically, the abbreviations represent the names of the amino acids in the order they are present. The amino acid cysteine (cys) has a sulfhydryl (SH) group as a side chain. Two sulfhydryl groups can react in the presence of oxygen to form a disulfide (S-S) bond. Two disulfide bonds connect the A and B chains together, and a third helps the A chain fold into the correct shape. Note that all disulfide bonds are the same length, but are drawn different sizes for clarity. Image Attribution: OpenStax Biology</p></div>
<p>The <a href="https://app.ulearngo.com/tutorials/introducing-genetics/gene-expression-2">gene</a> encoding every protein ultimately determines the unique sequence for the protein. A change in nucleotide sequence of the gene’s coding region may lead to a different amino acid being added to the growing polypeptide chain. This causes a change in protein structure and function.</p>
<h3>Hemoglobin molecule and sickle cell anemia</h3>
<p>In sickle cell anemia, the hemoglobin <em data-effect="italics">β</em> chain (a small portion of which you can see in the <a href="#attachment_95342">image below</a>) has a single amino acid substitution. This causes a change in protein structure and function. Specifically, valine substitutes the amino acid glutamic acid in the <em data-effect="italics">β</em> chain.</p>
<div class="wp-caption alignnone" id="attachment_95342" style="width: 611px"><a href="https://data.ulearngo.com/assets/421ffa3c-a049-4d0f-819f-db97e04d63a0"><img alt="hemoglobin-beta-chain" class="size-full wp-image-95342" height="394" src="https://data.ulearngo.com/assets/421ffa3c-a049-4d0f-819f-db97e04d63a0" width="611"/></a><p class="wp-caption-text">The beta chain of hemoglobin is 147 residues in length, yet a single amino acid substitution leads to sickle cell anemia. In normal hemoglobin, the amino acid at position seven is glutamate. In sickle cell hemoglobin, this glutamate is replaced by a valine. Image Attribution: OpenStax Biology</p></div>
<p>What is most remarkable to consider is that a hemoglobin molecule is made up of two alpha chains and two beta chains that each consist of about 150 amino acids. The molecule, therefore, has about 600 amino acids. The structural difference between a normal hemoglobin molecule and a sickle cell molecule—which dramatically decreases <a href="https://app.ulearngo.com/tutorials/introducing-study-of-life/what-is-life">life</a> expectancy—is a single amino acid of the 600. What is even more remarkable is that three nucleotides encode each of those 600 amino acids. But a single base change (point mutation), 1 in 1800 bases causes the mutation.</p>
<div class="wp-caption alignnone" id="attachment_95345" style="width: 535px"><a href="https://data.ulearngo.com/assets/9df7d499-7803-4c36-bf88-3ffd69dc096a"><img alt="normal-cells-vs-sickle-cells" class="size-full wp-image-95345" height="357" src="https://data.ulearngo.com/assets/9df7d499-7803-4c36-bf88-3ffd69dc096a" width="535"/></a><p class="wp-caption-text">In this blood smear, visualized at 535x magnification using bright field microscopy, sickle cells are crescent shaped (somewhat semicircular). Normal cells on the other hand, are disc-shaped. Image Attribution: Modification of work by Ed Uthman; scale-bar data from Matt Russell</p></div>
<p>Because of this change of one amino acid in the chain, hemoglobin <a data-lesson="first-organic-molecules" data-subject="biology" data-tutorial="evolution-overview" href="https://app.ulearngo.com/biology/evolution-overview/first-organic-molecules">molecules</a> form long fibers that distort the biconcave, or disc-shaped, <a data-lesson="red-blood-cells" data-subject="biology" data-tutorial="circulatory-system" href="https://app.ulearngo.com/biology/circulatory-system/red-blood-cells">red blood cells</a> and assume a crescent or “sickle” shape, which clogs arteries (<a href="#attachment_95345">see image above</a>). This can lead to myriad serious health problems such as breathlessness, dizziness, headaches, and abdominal <a data-lesson="thermoreception-and-pain" data-subject="biology" data-tutorial="sensory-systems" href="https://app.ulearngo.com/biology/sensory-systems/thermoreception-and-pain">pain</a> for those affected by this disease.</p>

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Primary Structure of Proteins

Biology studies life and living organisms. Biology can be divided into different sections that cover the morphology, physiology, anatomy, behavior, and so on of living organisms.

Biology

Discover the different types and functions of biological macromolecules including carbohydrates, lipids, proteins, and nucleic acids, and explore their structures and synthesis through lessons on hydrolysis, disaccharides, protein structures, and DNA double-helix.


Primary Structure of Proteins

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