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Quaternary Structure

Notes

Quaternary Structure

Sections

quaternary structure of proteins

  • Proteins that have multiple polypeptide chains have a quaternary structure, which forms from the combination of multiple polypeptide subunits.
  • Quaternary structure is the spatial arrangement of and interaction between polypeptide units. These subunits work together to form a complex oligomeric protein.
  • Quaternary structure molecular interactions are the same as those of tertiary structure: hydrogen and ionic bonds, hydrophobic interactions, and disulfide bonds.
  • Whereas tertiary interactions exist between amino acids of a single polypeptide chain, quaternary interactions exist between different polypeptide chains.

quaternary structure oligomers

The dimer is the simplest quaternary structure; it has just two subunits.

  • Homodimer with two identically shaped subunits
    – "homodimer" references the sameness of its subunits.
  • Heterodimer with two differently shaped subunits
    – "heterodimer" references the difference in its subunits.

Trimers have 3 subunits

  • We draw three interwoven strands to represent collagen, which is a homotrimeric protein.
  • Collagen polypeptides interweave to provide connective tissue with strength (just as a three-stranded rope is stronger than a single-stranded one).

Tetramers have 4 subunits

  • Alpha-2-beta-2 tetramer, which is a protein with four subunits, but with only two unique components.
  • Hemoglobin is an alpha-2-beta-2 tetramer; small changes in each of the subunits affects its oxygen carrying capacity.

Clinical correlation: Rhinovirus, which causes the common cold, has a viral coat of 240 subunits, with 60 copies of 4 different subunits.

The following four conformational changes can occur because of the multimeric nature of quaternary structure:

  • Changing the shape of one subunit results in a shift of the positions of all the other subunits to accommodate the change.
  • Changes in the shape of all of the subunits can cause a complete change in the structure of the protein (making it "open" or "closed" or "on" or "off").
  • The multiple sites for modifications, such as phosphorylation, allows for a wide range of functional states of the protein.
  • The ability for multiple molecules to bind all at once, or the same molecule in multiple positions, enhances the protein's functionality.

Full-Length Text

  • Here we will learn about the quaternary structure of proteins.
    • Proteins that have multiple polypeptide chains have a quaternary structure, which forms from the combination of multiple polypeptide subunits.
  • Start a table to denote some key quaternary structure features.
    • Quaternary structure is the spatial arrangement of and interaction between polypeptide units. These subunits work together to form a complex oligomeric protein.
    • Quaternary structure molecular interactions are the same as those of tertiary structure: hydrogen and ionic bonds, hydrophobic interactions, and disulfide bonds.
    • Whereas tertiary interactions exist between amino acids of a single polypeptide chain, quaternary interactions exist between different polypeptide chains.

With that information as a background, now let's draw some representative quaternary structure oligomers.

Start with the simplest quaternary structure: the dimer, we'll see that it has just two subunits.

  • First, draw a homodimer with two identically shaped subunits; "homodimer" references the sameness of its subunits.
  • Next, draw a heterodimer with two differently shaped subunits; "heterodimer" references the difference in its subunits.

Now, we'll draw a trimer, which has 3 subunits.

  • First, draw a trimer with three subunits.
  • Now, draw three interwoven strands to represent collagen, which is a homotrimeric protein.
    • Collagen polypeptides interweave to provide connective tissue with strength (just as a three-stranded rope is stronger than a single-stranded one).

Now let's draw a tetramer, which has 4 subunits.

  • First, draw a tetramer with two pairs of identical subunits, "alpha" and "beta," called: alpha-2-beta-2 tetramer, which is a protein with four subunits, but with only two unique components.
  • Indicate that hemoglobin is an alpha-2-beta-2 tetramer; small changes in each of the subunits affects its oxygen carrying capacity.
    • Enormous numbers of subunits can combine to form quaternary structure.
    • As a clinical correlation, indicate that rhinovirus, which causes the common cold, has a viral coat of 240 subunits, with 60 copies of 4 different subunits.

We've seen how quaternary structure can bring together multiple subunits to increase protein strength (eg, collagen), now let's see how it can bring together numerous subunits for a complex function, such as DNA replication.

  • Indicate that holoenzymes are enzymes with multiple subunits.
    • We'll use bacterial DNA polymerase 3 as an example, so we can get a better understanding of their complexity.

Draw DNA polymerase 3 as follows:

  • Draw two pincer-shaped alpha subunits that mirror each other.
  • Inside each pincer draw a small epsilon subunit.
  • Then, draw smaller theta subunit on top of it.
  • At the bottom of each pincer, attach a tau unit (like arms).
  • Then, connect the two tau units with a gamma subunit.
  • Below the gamma subunit, draw a psi subunit, and a delta subunit next to it.
  • Finally, draw a chi subunit below the psi subunit.
  • Then, draw a delta prime subunit next to it, which is also attached to the theta subunit.
  • Although this enzyme has numerous subunits, each one plays its own important role in bacterial DNA replication.

So we've seen how multiple subunits can increase a protein's strength (collagen), its function (as in DNA polymerase 3), now let's see how it allows for numerous conformational changes.

  • Indicate that the following four conformational changes can occur because of the multimeric nature of quaternary structure:
    • Changing the shape of one subunit results in a shift of the positions of all the other subunits to accommodate the change.
    • Changes in the shape of all of the subunits can cause a complete change in the structure of the protein (making it "open" or "closed" or "on" or "off").
    • The multiple sites for modifications, such as phosphorylation, allows for a wide range of functional states of the protein.
    • The ability for multiple molecules to bind all at once, or the same molecule in multiple positions, enhances the protein's functionality.

Let's draw a simple example of this.

  • Draw a simple protein with no quaternary structure.
    • This means that the protein only has one polypeptide chain, instead of subunits.
  • Now redraw our simple protein with a phosphate group attached.
    • Remember that phosphate groups induce conformational changes in a protein, which affects its function. Thus by phosphorylating the protein, we can have two possible states.
  • Indicate that:
    • 0 = without the phosphate
    • 1 = with the phosphate.
  • Now draw a heterodimer, with subunits a and b.
    • Indicate that if both subunits can be phosphorylated, we have just doubled the number of possible conformations of the protein: a0b0, a1b0, a0b1 and a1b1 (using the same notation as before where 1 is phosphorylated and 0 is unphosphorylated).

Let's draw this.

  • Indicate that the heterodimer that we have already drawn is a0b0, where both subunits are unphosphorylated.
  • Next, draw a1b0: draw our heterodimer where subunit a is phosphorylated and subunit b is not.
  • Now, draw a0b1: draw our heterodimer with subunit b phosphorylated and "a" unphosphorylated.
  • Finally, draw a1b1: draw the heterodimer with both subunits phosphorylated.
  • If each of these represents a change in the functional ability of the protein, then just having two subunits instead of one, our protein can do twice as much.

What about if we had three subunits, how many possible conformations will we have? Let's find out.

  • Write out the possible conformations for a protein with subunits, a, b, and c.
  • Indicate the following:
    • If no subunits are phosphorylated, we have: a0-b0-c0.
  • Now let's phosphorylate one subunit at a time.
    • a1-b0-c0
    • a0-b1-c0
    • a0-b0-c1
  • And if we phosphorylate two subunits at a time. We add the possible conformations
    • a1-b1-c0
    • a1-b0-c1
    • a0-b1-c1
  • And of course, we can phosphorylate all three so that we have
    • a1-b1-c1
  • Indicate that, in total, we have 8 possible conformations!
    • This computational exercise, albeit a simplification of the multiplicity of quaternary structure, illustrates the complexity and potential power of multimeric structure proteins.