View source for User:Stephen Mills/Secondary Structure: Helices

== Biochemistry Tutorial #2 - Secondary Structure (Part 1) ==

The secondary structure of a protein is defined by the local conformation of its backbone (polypeptide mainchain). There are two major types of regular secondary structures in proteins: helices and sheets. There are also regular turn structures. Turns often connect one element of secondary structure to another in the overall fold of the protein. Other parts of the protein mainchain may adopt more irregularly defined loops. This tutorial will focus mainly on helices and sheets.

''Note: in these tutorials, the images are 3D interactive images. You can manipulate them as you wish to get a better view of the molecules.'' 

You can rotate the structures by holding down the right mouse button and dragging. At any time you can click the 'toggle spin' button in box to stop/start the structure spinning.

Other things you can do:
::To rotate: left drag
::To Zoom: scroll button or shift + left drag
::To Translate: ctrl + right drag
::Right click to bring up an options menu

==Helices==

In helices, the polypeptide mainchain twists into a path that resembles a spiral staircase. Just like spiral staircases, helices come in different forms, depending on how tightly twisted the mainchain is. The form of a helix can be described by parameters such as the number of steps (amino acids) it takes to complete a turn (a 360<sup>o</sup> rotation around the long axis of the helix), and how far you travel along the helix axis in one complete turn. Helices can also be left-handed or right-handed. For proteins composed of L-amino acids, helices are almost always right-handed (a notable exception is the type I poly-proline helix). Although several types of helix form are possible, two regular helices are very common in proteins: the α-helix and the 3<sub>10</sub>-helix.

==The α-helix==

α-helices are the most common type of regular helix found in proteins. They are characterized by the following helix parameters:
::Dihedral angles: Φ ~ -60<sup>o</sup>, φ ~ -45<sup>o</sup>
::Repeat (number of residues per turn) = 3.6
::Rise (translation along axis per amino acid residue) = 1.5 Angstroms (0.15 nm)
::Twist (rotation around axis per amino acid residue) = 100<sup>o</sup> (= 360<sup>o</sup>/repeat)
::Pitch (translation along axis per turn) = 5.4 Angstroms (= 0.54 nm = Repeat x Rise)

The helix shown below is a 19 amino acid chain in α-helical conformation. 
<Structure load='Tut_alpha_helix.pdb' size='500' frame='true' align='left' caption='' scene='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_load/1' name='initial_alpha_helix'/>

All the atoms are shown in this initial orientation (C = green; N = blue; O = red; S = yellow; H = white). The helix axis runs vertically, approximately parallel to the plane of the screen.<br/>
<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_load/1' target='initial_alpha_helix'>Click here</scene> to go back to the initial view.<br/>

<scene name='User:Stephen_Mills/Secondary_Structure:_Helices/A_helix_load/1' target='initial_alpha_helix'>Click here</scene> to show the helix in a space-filling representation. This representation shows the atoms with a radius that is approximately correct.

<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_mainchain/3' target='initial_alpha_helix'>Click here</scene> to show only the polypeptide mainchain (NH, Cα, and C=O).

Identify the N- and C-termini. <scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_mainchain_label/4' target='initial_alpha_helix'>Click here to see if you were correct.</scene> 

<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_mainchain_label_ribbon/3' target='initial_alpha_helix'>Click here to add a ribbon that will help show the path of the mainchain. </scene> You should be able to see that it is helical with a right-handed twist (you rotate to the right as you move along the helix axis).

Click the "toggle spin" button in the box to stop the structure from rotating. Now use your mouse to rotate the structure to look down the helix axis. If you have any problems with finding this view, <scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_mainchain_label_axis/3' target='initial_alpha_helix'>click here </scene>to zoom in and look down the helix axis from the N-terminal end.
<br/><br/>
What is in the middle of the helix?
<br/><br/>
Now, 
<scene name='User:Stephen_Mills/Secondary_Structure:_Helices/A_helix_main_axis_spacefill/1' target='initial_alpha_helix'>click here</scene> to see the helix in a space-filling representation.<br/><br/>

Now, answer that question again - what is in the middle of the helix?
<br/><br/><br/><br/><br/><br/><br/><br/><br/><br/><br/><br/><br/><br/><br/>

==H-Bonding in α-helices==
<Structure load='Tut_alpha_helix.pdb' size='500' frame='true' align='left' caption='' scene='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_mainchain_label/4' name='Hbonds'/>
I'll reset the structure for you. Now, look at the structure carefully and identify the mainchain NH and C=O groups. What is the orientation of these groups with respect to the helix axis?

<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_mainchain_label_hbonds/10' target='Hbonds'>Click here to zoom in a little and add hydrogen bonds for the mainchain (dashed lines).</scene> The hydrogen bonds connect backbone NH groups and C=O groups. The N-H group is the hydrogen bond donor, the oxygen in the C=O group is the acceptor (N-H--->O=C). Each hydrogen bond is approximately 3.0 Angstroms (0.3 nm) in length (measured between the N and the O). These hydrogen bonds connect amino acids that are spaced 4 residues apart in the primary sequence. The NH group is from amino acid X and the O is from amino acid X-4 (where X is the number of the amino acid in the sequence).


<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_mainchain_label_hbonds/9' target='Hbonds'>Click here to zoom out again.</scene> You should be able to see that all of the mainchain NH and C=O groups are involved in hydrogen bonds. This is possible because 1) all the mainchain NH groups and C=O groups are parallel to the helix axis, 2) all the NH groups point toward the N-terminus of the helix, and 3) all the C=O groups point toward the C-terminus. Only the NH groups in the first (N-terminal) turn, and the C=O groups in the last (C-terminal) turn of the helix do not have hydrogen bonding partners. However, if this helix were part of a larger protein, these groups would participate in hydrogen bonds with other parts of the protein. This is called 'helix capping' and the other groups involved are typically from amino acid side chains (that are called 'helix capping residues').

<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_sidechains/3' target='Hbonds'>Click here to show the side chains again.</scene> The atoms of each amino side chain have been colored light blue to show them more clearly. <scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_sidechains_axis/1' target='Hbonds'>Click here to change the view to look down the helix axis.</scene>

What is the general orientation of the side chains with respect to the helix axis? You should observe that each side chain points away from the helix axis, but points down toward the N-terminus of the helix (this is clearer if you only show the first bond of each side chain: <scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_sidechains_cropped/1' target='Hbonds'>click here</scene> or <scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/A_helix_sidechains_cropped/2' target='Hbonds'>click here</scene>).
<br/><br/><br/><br/><br/>

==The 3<sub>10</sub>-helix==

3<sub>10</sub>-helices are also found in proteins but are less common than α-helices. They are characterized by the following helix parameters:
::Dihedral angles: Φ ~ -49<sup>o</sup>, φ ~ -26<sup>o</sup>
::Repeat (number of residues per turn) = 3.0
::Rise (translation along axis per amino acid residue) = 2.0 Angstroms (0.2 nm)
::Twist (rotation around axis per amino acid residue) = 120<sup>o</sup> (= 360<sup>o</sup>/repeat)
::Pitch (translation along axis per turn) = 6.0 Angstroms (= 0.6 nm = Repeat x Rise)

The helix shown below is a 19 amino acid chain in 3<sub>10</sub>-helical conformation. 
<Structure load='Tut_3-10_helix.pdb' size='500' frame='true' align='left' caption='' scene='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_load/4' name='310_helix'/>

All the atoms are shown in this initial orientation (C = green; N = blue; O = red; S = yellow; H = white). The helix axis runs vertically, approximately parallel to the plane of the screen.

<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_mainchain/2' target='310_helix'>Click here</scene> to show only the polypeptide mainchain (NH, Cα, and C=O). The N- and C-termini are labeled.

<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_mainchain_ribbon/2' target='310_helix'>Click here to add a ribbon that will help show the path of the mainchain. </scene> You should be able to see that just like the α-helix, it is helical with a right-handed twist, and again, all the mainchain NH groups point toward the N-terminus, and all the mainchain C=O groups point toward the C-terminus.

The difference between an α-helix and a 3<sub>10</sub>-helix lies in the helix parameters. A 3<sub>10</sub>-helix is more tightly twisted so that the mainchain completes one turn every 3 amino acids (instead of 3.6 for the α-helix). This also results in a larger rise and pitch so that the 3<sub>10</sub>-helix is longer than an α-helix (of the same number of residues).

<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_mainchain_axis/1' target='310_helix'>Click here </scene>to zoom in and look down the helix axis from the N-terminal end. You'll be able to see the triangular shape of the mainchain. 
<br/><br/><br/><br/><br/><br/><br/><br/><br/><br/>

==H-Bonding in 3-10 Helices==
<Structure load='Tut_3-10_helix.pdb' size='500' frame='true' align='left' caption='' scene='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_mainchain_hbonds/1' name='310_hbonds'/>
I've zoomed back out and turned on the hydrogen bonds for the mainchain. Once again, all of the mainchain NH and C=O groups are involved in hydrogen bonds. However, now the hydrogen bonds connect amino acids that are spaced 3 residues apart in the primary sequence. The NH group is from amino acid X and the O is from amino acid X-3 (where X is the number of the amino acid in the sequence). <scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_mainchain_hbonds/2' target='310_hbonds'>Click here</scene> to zoom in and you should be able to see this more clearly.

<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_sidechains/1' target='310_hbonds'>Click here to zoom out and show the side chains again.</scene> The atoms of each amino side chain have been colored light blue to show them more clearly. <scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_sidechains_axis/2' target='310_hbonds'>Click here to change the view to look down the helix axis.</scene>

As for the α-helix, each side chain points away from the helix axis, and points down toward the N-terminus of the helix. However, because the 3<sub>10</sub>-helix repeat parameter is an integer (= 3.0), the side chains are spaced 120<sup>o</sup> apart and form 3 distinct sides to the helix. You'll see this more clearly if the side chains are colored in groups to show this (residues 1,4,7,10 etc are blue; residues 2,5,8,11 etc are purple; residues 3,6,9,12 etc are yellow): <scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_sidechains_tricolor/1' target='310_hbonds'>click here to look from the side</scene> or <scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_sidechains_tricol_ax/1' target='310_hbonds'>click here to view down the helix axis</scene>.

<scene name='User:Robert_Dutnall/Sandbox_1_alpha_helix/310_helix_load/4' target='310_hbonds'>Click here to reset the view of the helix.</scene>

'''What is the identity of the N-terminal amino acid?'''

'''What is the identity of the C-terminal amino acid?'''

'''Write down these answers so that you can submit them to your instructor at the end of this tutorial.'''

[[User:Stephen_Mills/Secondary_Structure:_Sheets|Click here to go on to part 2 of this tutorial.]]

[[User:Stephen_Mills/Biochemistry_Tutorials|Click here to go back to the main Tutorial page.]]

== Files for 3D printer == 
<i class="fas fa-cubes"></i> An protein alpha helix in different representations by [[User:Marius Mihasan|Marius Mihasan]] [https://3dprint.nih.gov/discover/3dpx-014891  <i class="fas fa-download"></i>]
[[Category:3D printer files]]