64 - Protein Structure I (w/ Shannon Speer!)
64. Protein Structure I
After an episode about lipids and nucleic acids, it’s time to forget about sugars and talk about my favorite biomolecules: proteins. What are amino acids? What are some protein functions? Why do proteins’ structure often inform their function? Let’s learn to be scientifically conversational.
General Learning Concepts
1) What is a protein?
a. What is a fundamental biomolecule? Major classes of fundamental biomolecules include amino acids (proteins), carbohydrates (sugars / starches), lipids (fats and oils), and nucleotides (nucleic acids).
b. What is an amino acid? “Amino acids are any of a group of organic molecules that consist of a basic amino group (-NH2), an acidic carboxyl group (-COOH), and an organic R group (or side chain), which is unique to each amino acid.”
c. What is a protein? “Proteins are complex molecule composed of amino acids and necessary for the chemical processes that occur in living organisms. Proteins are basic constituents in all living organisms. Their central role in biological structures and functioning was recognized by chemists in the early 19th century when they coined the name for these substances from the Greek word proteios, meaning ‘holding first place.’”
d. What are some functions of proteins? Transporting and moving other molecules, catalyzing chemical reactions, degrading other molecules / organisms, binding to other molecules for neutralization, acting as scaffolds for parts of the cell, providing movement within single cells, signaling to other cells or parts of the single cell…
2) Why does protein structure matter?
a. Structure/function relationships: The three-dimensional shape of each protein is perfectly suited to perform one specific function. For example, aquaporins are channel proteins that form small tunnels through a cell membrane. The internal surface of aquaporin tunnels possesses a specific diameter and polarity. This structure is perfectly designed to transport water molecules but very little else, providing specificity and function. If protein structure changes, so does a protein’s ability to function.
b. Structure:
i. Primary: All proteins are composed of small subunits called amino acids that are joined together like links in a chain to make large complex protein structures. There are twenty different types of amino acids that can be linked together in various orders and frequencies. Every type of protein is made of a different and unique sequence of amino acids.
ii. Secondary: A protein's primary structure is the specific order of amino acids that have been linked together to form a polypeptide chain. But polypeptides do not simply stay straight as liniar sequences of amino acids. The fold back on themselves to create complex 3-dimensional shapes.
iii. Tertiary: A protein needs to adopt a final and stable 3-dimensional shape in order to function properly. The Tertiary Structure of a protein is the arrangement of the secondary structures into this final 3-dimensional shape.
iv. Quaternary: Some proteins are made up of more than one amino acid chain, giving them a quaternary structure. These multi-chain proteins are held together with the same forces as the tertiary structure of individual protein chains (hydrophobic, hydrophilic, positive/negative and cysteine interactions). Sometimes the various protein chains in a protein complex are identical and other times they are each unique.
3) Fun Tidbits
a. The Anfinsen Experiment: Anfinsen's work showed convincingly that proteins can indeed adopt their native information spontaneously, i.e. sequence determines structure. Christian Anfinsen was awarded the 1972 Nobel Prize in Chemistry with Stanford Moore and William Howard Stein for the connection between amino acid sequence and biologically active conformations of ribonuclease.
b. Humans cannot produce all amino acids: “Humans can produce 10 of the 20 amino acids. The others must be supplied in the food. Failure to obtain enough of even 1 of the 10 essential amino acids, those that we cannot make, results in degradation of the body's proteins—muscle and so forth—to obtain the one amino acid that is needed. Unlike fat and starch, the human body does not store excess amino acids for later use—the amino acids must be in the food every day.”
4) Solicited Questions
a. What is Levinthal’s Paradox? Levinthal's paradox is that finding the native folded state of a protein by a random search among all possible configurations can take an enormously long time. Yet proteins can fold in seconds or less.