Super-Secondary Structure

Sections

Full-Length Text

super-secondary structures

• Complex, three-dimensional structures, that still involve localized amino acid sequences close to each other.
• Super-secondary structure comprises localized motifs of secondary structures, which are combinations of alpha helices, beta sheets, or both alpha helices and beta sheets.
• Motifs give proteins unique structural features that enable their unique function. Motifs provide unique shapes that enable proteins to bind DNA, metals, substrates, cofactors or other proteins.

eight of the most common super-secondary structures

Alpha helices

• Helix-turn-helix
• Helix-loop-helix
• Coiled-coil

Beta motifs

• Beta-hairpin
• Greek key
• Beta barrel.

Combination motifs

• Beta-alpha-beta
• Zinc finger

alpha helices

• Most alpha helices bind DNA.

Helix-turn-helix (or HTH for short)

• We connect two helices with a short sequence of amino acids. As the name implies, a helix-turn-helix is two helices connected by a short sequence, or turn of amino acids.
• A turn is a short sequence of 4 to 6 amino acids, which are usually positively charged.
• The helix-turn-helix motif binds DNA. In fact, this motif was discovered by comparing sequences of genes that encode regulatory proteins for transcription.

Helix-loop-helix (or bHLH for short)

• We connect two helices with a sequence of amino acids.
• Similar to the HTH, the helix-loop-helix is two helices connected by a short sequence, or loop of amino acids that is longer than a turn.
• Loops are considerably longer sequences of amino acids than turns.
• The helix-loop-helix is a DNA-binding motif commonly found in transcription factors, such as the EF-hand, a calcium-binding domain common to calcium-binding proteins.

Coiled-coil domain

• Two alpha helices that wind around each other.
• The coiled coil domain comprises at least two alpha helices that wrap around each other.
• Coiled coil domains also bind DNA and their individual helices have heptad repeats. For instance, the leucine zipper has a leucine residue that repeats every seventh amino acid.

Again, all three of these alpha helices are DNA-binding domains; in fact almost all DNA-binding domains are helix-rich.

beta-strand super-secondary structures

The beta hairpin

• This is the simplest. We join two antiparallel beta strands with a short loop. These two strands form a hairpin shape, hence the name: beta hairpin.
• Proline and glycine residues are common in the turn because their structure is favored for the sharp angle of the turn.

The Greek key

• A more complex beta motif. We draw four beta strands in the following orientation: up, down, up, down. As you may imagine, we can connect these in a variety of ways using loops of different lengths.
• In the Greek key motif, the strands are in the following order: 3, 2, 1, 4. This pattern is characteristic of and unique to the Greek key motif.
• We draw loops to connect the arrows in the order that we have just outlined.
• The N-terminal end precedes beta strand 1 and the C-terminal end comes after beta strand 4.

The Beta Barrel

• The most complex of the beta sheet structures. We draw 9 antiparallel beta strands diagonally in a barrel shape. Beta barrels can also contain alpha helices to help dictate their structure, but we have chosen the simplest form of the beta barrel to draw here, the up-and-down beta barrel.
• As you can imagine, the barrel shape can be made with several variations, which have different names, such as the Greek key barrel and the jellyroll.
• Beta barrels are commonly found in proteins that transport ions across cell membranes, called porins.

two of the motifs that contain both alpha helices and beta sheets

The beta-alpha-beta motif

• We draw a beta strand linked to an alpha helix, which itself is linked to another beta strand which runs parallel to the first. This structure allows for adjacent parallel beta strands.
• The beta-alpha-beta motif is often found in parallel sections of beta sheets.
• Beta-alpha-beta motifs are almost always right-handed, meaning the loops and helix have a right-handed twist.

The zinc finger

• It combines two beta strands and an alpha helix. We draw a pair of antiparallel beta strands, which are connected to an alpha helix that runs perpendicular to the beta strands.
• We draw a zinc atom in the space created by these three elements and dash lines to represent the bonds between the zinc and the polypeptide sequences. This is our zinc finger, a zinc-containing motif that looks kind of like zinc is being held between fingers.
• The Cys2His2 zinc finger motif is one of the most common of the zinc fingers and gets its name because two cysteine and two histidine residues form the four bonds to the zinc atom.

Full-Length Text

• Here we will learn about how combinations of secondary structures in close proximity to each other form super-secondary structures.
  • Although these are complex, three-dimensional structures, they still involve localized amino acid sequences close to each other.
  • We will learn a few of the most common super-secondary structures and some examples of their functional applications.

• Start a table, so we can keep track of some key features of super-secondary structures.

• Denote that super-secondary structure comprises localized motifs of secondary structures, which are combinations of alpha helices, beta sheets, or both alpha helices and beta sheets.

• Denote that motifs give proteins unique structural features that enable their unique function.
  • Motifs provide unique shapes that enable proteins to bind DNA, metals, substrates, cofactors or other proteins.

In this tutorial we will cover eight of the most common super-secondary structures.

• The first category we'll address are the alpha helices –
  • Helix-turn-helix
  • Helix-loop-helix
  • Coiled-coil

• Next, the beta motifs –
  • Beta-hairpin
  • Greek key
  • Beta barrel

• Lastly, the combination motifs –
  • Beta-alpha-beta
  • Zinc finger

Let's begin with the super-secondary structures of alpha helices.

Specifically, let's first address the helix-turn-helix (or HTH for short).

• Connect two helices with a short sequence of amino acids.
  • As the name implies, a helix-turn-helix is two helices connected by a short sequence, or turn of amino acids.

• Indicate that a turn is a short sequence of 4 to 6 amino acids, which are usually positively charged.

• Denote that the helix-turn-helix motif binds DNA.
  • In fact, this motif was discovered by comparing sequences of genes that encode regulatory proteins for transcription.

Next, we will draw a basic helix-loop-helix (or bHLH for short).

• Connect two helices with a sequence of amino acids.
  • Similar to the HTH, the helix-loop-helix is two helices connected by a short sequence, or loop of amino acids that is longer than a turn.

• Indicate that a loop is 12 to 17 amino acids.
  • Amino acids in the loop also tend to be positively charged as they do in the HTH.

• Denote that the helix-loop-helix is a DNA-binding motif commonly found in transcription factors, such as the EF-hand, a calcium-binding domain common to calcium-binding proteins.

Now, let's draw the coiled-coil domain.

• Draw two alpha helices that wind around each other.
  • As the name implies, the coiled coil domain comprises at least two alpha helices that wrap around each other.

• Write that coiled coil domains also bind DNA and their individual helices have heptad repeats.
  • For instance, the leucine zipper has a leucine residue that repeats every seventh amino acid.
  • Notice that all three of these are DNA binding domains; in fact almost all DNA-binding domains are helix-rich.

Now let's look at beta-strand super-secondary structures. First, the beta hairpin, which is the simplest.

• Join two antiparallel beta strands with a short loop.
  • These two strands form a hairpin shape, hence the name: beta hairpin.

• Write that beta hairpins can be found alone or as part of a beta sheet.

Challenge yourself to think about an amino acid that would be commonly found in that sharp turn of the hairpin…

• Write that proline and glycine residues are common in the turn, specifically, because their structure is favored for the sharp angle of the turn.

Now let's learn the Greek key, a more complex beta motif.

• Draw four beta strands in the following orientation: up, down, up, down.
  • As you may imagine, we can connect these in a variety of ways using loops of different lengths.

• Indicate that in the Greek key motif, the strands are in the following order: 3, 2, 1, 4.
  • This pattern is characteristic of and unique to the Greek key motif.

• Then, draw loops to connect the arrows in the order that we have just outlined.

• Indicate that the N terminal end precedes beta strand 1 and the C terminal end comes after beta strand 4.

Next, let's draw the beta barrel, which is the most complex of the beta sheet structures.

• Draw 9 antiparallel beta strands diagonally in a barrel shape.
  • Beta barrels can also contain alpha helices to help dictate their structure, but we have chosen the simplest form of the beta barrel to draw here, the up-and-down beta barrel.

Next, connect our strands to make this beta barrel as follows:

• Starting with the left-most beta strand, at the front of the barrel, connect the beta strands sequentially.

• Denote that a beta barrel is a complex beta sheet structure.
  • As you can imagine, the barrel shape can be made with several variations, which have different names, such as the Greek key barrel and the jellyroll.

• Write that beta barrels are commonly found in proteins that transport ions across cell membranes, called porins.

Next, we will draw two of the motifs that contain both alpha helices and beta sheets. Begin with the beta-alpha-beta motif.

• Draw a beta strand linked to an alpha helix, which itself is linked to another beta strand which runs parallel to the first.
  • This structure allows for adjacent parallel beta strands.

• Denote that the beta-alpha-beta motif is often found in parallel sections of beta sheets.

• Also write that beta-alpha-beta motifs are almost always right-handed, meaning the loops and helix have a right-handed twist.

Lastly, we will draw the zinc finger, which combines two beta strands and an alpha helix.

• Draw a pair of antiparallel beta strands, which are connected to an alpha helix that runs perpendicular to the beta strands.

• Now draw a zinc atom in the space created by these three elements and dash lines to represent the bonds between the zinc and the polypeptide sequences.
  • This is our zinc finger, a zinc-containing motif that looks kind of like zinc is being held between fingers.

• Indicate that this is a Cys2His2 zinc finger motif.
  • It gets its name because two cysteine and two histidine residues form the four bonds to the zinc atom.

• Write that zinc fingers have a variety of shapes and structures.
  • The one that we have drawn, the Cys2His2, is one of the most common of these.

• Write that zinc fingers also bind DNA, like our helix-turn-helix, helix-loop-helix and coiled coil domains do.