Secondary Structure 1: The Alpha Helix Endocrine System > Protein Metabolism > Protein Metabolism SECONDARY STRUCTURE: GENERAL CHARACTERISTICS The polypeptide chain begins to assume local 3D conformations of amino acids that are in close proximity with each other in their linear sequence. Here, we address the characteristics of one of the two major types of secondary structure: alpha helices. Secondary structure is the conformation of local segments of the polypeptide chain into three-dimensional structure. It specifically involves interactions between residues that are near each other along the polypeptide sequence. • Secondary structure includes: alpha helices and beta sheets. - Beta sheets are the most prominent secondary structures in proteins because they are the most stable. • Amino and carboxy groups of amino acid residues (the backbone of the polypeptide chain) form hydrogen bonds to create secondary structure. • Secondary structure involves backbone interaction and not side chain interactions. HYDROGEN BONDING: REVIEW We draw an NH group and a C-double-bond O-group. • Hydrogen bonds are formed in the presence of two electronegative atoms where one of the atoms has a hydrogen attached to it and the other has a lone pair of electrons. We dash a line from the hydrogen of the NH group to the oxygen of the CO group to depict a hydrogen bond. The nitrogen atom acts as a hydrogen donor (since it has the hydrogen atom attached to it*) The oxygen atom acts as the hydrogen bond acceptor (since the hydrogen bond is created with this atom*) GENERAL CHARACTERISTICS OF ALPHA HELICES • The carboxyl group on one amino acid forms a hydrogen bond with the amino group of the amino acid four residues down the chain, which is denoted as i + 4 -> i hydrogen bonding [i plus 4 to i hydrogen bonding]. This form of hydrogen bonding gives alpha helices their structure and shape. Thus, i +4 -> i hydrogen bonding means that amino acid 1 is hydrogen bonded to amino acid 4, 2 to 5, etc. We show a right-handed helix [To figure out which direction is right-handed, we make a thumbs-up with our right hand and look at the direction that the fingers curve]. • In an alpha helix all of the amino acid side chains face the outside of the helix because this is the most energetically stable arrangement. DISTANCE BETWEEN TURNS The distance between turns in the alpha helix is called the pitch and is 3.6 amino acid residues and measures 5.4 angstroms. 1 / 7 To discover where this value comes from, we do the following: - Each amino acid in the helix rotates it 100 degrees. - To complete a full turn of (360 degrees), 3.6 amino acids must be present. - In an alpha helix with ten turns, 36 amino acids exist. - The typical alpha helix is ~ 10 amino acids long. - 10 divided by 3.6 is ~ 2 .75 (2.78 to be more exact). • The rise is the distance between amino acids: it's a distance of 1.5 angstroms. • The pitch is the distance between the turns: it's 5.4 angstroms. To calculate this, we multiply the rise of the helix (1.5) by the number of residues per turn (3.6), which is 5.4. 5 FAVORABLE AMINO ACIDS IN ALPHA HELICES: M-A-R-K-L • MARKL for: methionine, alanine, arginine, lysine and leucine. - Methionine (M) - Alanine (A) - Arginine (R) - Lysine (K) - Leucine (L) • The side chains of these amino acids are relatively small and relatively simple, which would preclude steric clashes. UNFAVORABLE AMINO ACIDS IN ALPHA HELICES • Unfavorable because of size/charge/shape of side chains, , which can destabilize helices. • They include: proline, glycine, serine, aspartate, asparagine, threonine, valine and isoleucine. Proline • Helix breaker • Amino group cannot H-bond --> ring-structure • Does not allow for 100 degree rotation • Is found at beginning/end of helices: proline is a good amino acid to begin an alpha helix because of the rigidity of its structure. - We label the first amino acid in our alpha helix as proline as a helpful reminder. Glycine 2 / 7 • Unfavorable in a helix because it has so many angles of rotation. • It's conformationally flexible because it lacks a true side chain (since its R-group is a hydrogen atom), which means the amount of variability makes it energetically expensive for glycine to adopt the alpha-helical structure. Beta-branched side chains: threonine, valine and isoleucine (TVI) • Beta-branched side chains mean there's a branch at the beta carbon of the amino acid: the first carbon on its side chain. As a result, they are favored in beta sheets. We remember this by the mnemonic "trees, "v"'s, and ice cracks". All of these have BRANCHES. Polar side chains: serine, aspartate and asparagine (NSD) • May also form H-bonds with backbone amino/carboxy groups. FULL-LENGTH TEXT • Here we will focus on the secondary structure of proteins, in which the polypeptide chain begins to assume local 3D conformations of amino acids that are in close proximity with each other in the linear sequence. - In this tutorial, we will learn about the characteristics of one of the two major types of secondary structure: alpha helices. • Start a table. • Denote that secondary structure is the conformation of local segments of the polypeptide chain into three-dimensional structure. - Secondary structure specifically involves interactions between residues that are near each other in the polypeptide sequence. • Denote that secondary structure includes, most notably, alpha helices and beta sheets. - These are the most prominent secondary structures in proteins because they are the most stable. • Denote that amino and carboxy groups of amino acid residues (the backbone of the polypeptide chain) form hydrogen bonds to create secondary structure. - It is important to note that secondary structure involves backbone interaction and not side chain interactions. 3 / 7 Before we draw our secondary structures, let's quickly review hydrogen bonding. • Draw an NH group and a C-double-bond O-group. - Hydrogen bonds are formed in the presence of two electronegative atoms where one of the atoms has a hydrogen attached to it and the other has a lone pair of electrons. • Label the nitrogen as the H-bond donor; in a hydrogen bond, the nitrogen atom acts as a hydrogen donor, since it has the hydrogen atom attached to it. • Then, label the oxygen atom as the H-bond acceptor; the oxygen atom acts as the hydrogen bond acceptor, since the hydrogen bond is created with this atom. • Now, dash a line from the hydrogen of the NH group to the oxygen of the CO group to depict a hydrogen bond With that knowledge of secondary structure and that review of hydrogen bonding, now, let's draw the alpha helix. Alpha helices were the first secondary structure proposed by Linus Pauling and Robert Corey in 1951. • Write that in an alpha helix, the carboxyl group on one amino acid forms a hydrogen bond with the amino group of the amino acid four residues down the chain, which is denoted as i + 4 to i hydrogen bonding. - This form of hydrogen bonding gives alpha helices their structure and shape. • Next, draw a right-handed helix. - To figure out which direction is right-handed, make a thumbs-up with your right hand and look at the direction that your fingers curve. The helix should go in that direction, if it is going upwards towards your thumb. • Attach R groups to the outside of the helix. - In an alpha helix all of the amino acid side chains face the outside of the helix because this is the most energetically stable arrangement. Now, let's learn about the distance between turns in the alpha helix. • Draw a line spanning the distance between the first and second turn and write that this distance is 3.6 amino acid residues. Let's discover where this distance comes from. • Write that each amino acid in the helix rotates it 100 degrees. - Thus, in order to complete a full turn of (360 degrees, how many amino acids must be present? 3.6. 4 / 7 - So how many amino acids exist in an alpha helix with ten turns? 10 x 3.6 equals 36 amino acids. • Now, write that alpha helices may range in length from 4 to over 40 amino acids but the typical alpha helix is about 10 amino acids long. - So how many turns exist in the typical alpha helix? 10 divided by 3.6, which is roughly 2 and 3/4 (2.78 to be more exact). With these knowledge points in mind, let's draw a second helix to show some additional characteristics. • Use circles linked by lines to construct our helix to draw a second alpha helix. - The circles represent each amino acid in the helix. - Don't forget to draw about three-and-a-half amino acids per turn! • Dash lines to show "i +4 to i hydrogen bonding". - This means that amino acid 1 is hydrogen bonded to amino acid 4, 2 to 5, etc. • Label the rise of the helix as the distance between the first and second amino acid, which is a distance of 1.5 angstroms - It is the same between each amino acid in the helix. • Label the pitch of the helix as distance between the first and second turn of the helix, which is 5.4 angstroms. How would we calculate this on our own? Multiply the rise of the helix (1.5) by the number of residues per turn (3.6), which is 5.4. Since the structure of the alpha helix is so uniform and amino acid side chains are so diverse in their sizes and characteristics, you can imagine that some amino acids are more favorable in alpha helices than others.