Protein Structure

 Molecular structure Textbook reference: Chapter 4 – pp. 71-79 (selected

 Peptide bonds sections as outlined below).
 Levels of protein structure Please work through these interactive online lecture notes
 Protein folding before attending Lecture 4.

Of all the macromolecules, proteins are the most versatile. Almost every process that occurs in a
cell requires proteins. So, apart from having complex structures, proteins also have a variety of
functions.
 Structural proteins - can aggregate to help define a cell’s shape and fix organelles in
position.
 Pores and channels – are proteins inserted in cell membranes that allow ions and small
molecules to pass through.
 Enzymes – are proteins that catalyze metabolic reactions in cells
 Signaling proteins – help cells communicate with each other to coordinate function

Molecular Structure
Background textbook reading:
 Section 4.1 Molecular Structure of Proteins (pp. 71-73)

Proteins are typically very large molecules. They are polymers of amino acids linked together by
peptide bonds. What type of bonds are peptide bonds? Covalent
An amino acid has a general structure shown below. Label the following on the diagram: R-group
(the R group changes between each amino acid), amino group, alpha (α) carbon (central carbon),
carboxyl group
Alpha carbon The three-dimensional structure of an amino acid looks
like this.
carboxyl
Amino group group

R group

What is the difference between illustrations ‘a’ and ‘b’ on the right? Explain.

In order to maintain the pH of 7.35-7.45 the carboxyl group in illustration ‘b’ lost a proton it has been deprotonated and th

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It is the R-group that makes each amino acid unique. R-groups are chemically diverse and give
amino acids their properties, so amino acids are typically classified according to the properties of
their R-groups. These properties strongly influence protein structure such as how proteins fold
(i.e. their three-dimensional structure).
There are 20 amino acids that are the building blocks of all proteins.

Using Figure 4.2 on p. 73 of your textbook, complete the graphic below to summarize which
amino acids belong to which category.

Hydrophilic Amino Acids Hydrophobic

Amino Acids (has
lots of carbons and
Basic Acidic Polar hydrogens no Special Amino Acids
(positively (negatively (uncharged) functional groups
that add polarity) Glycine – small and only has a H
charged) charged)
Asparagine as the R group
Lysine Aspartic acid Glutamine Alanine Proline – has a carbon ring?
Serine Valine Cysteine – has sulfhydral group
Arginine Glutamic Threonine Leucine
acid Isoleucine
Histidine
Methionine
Phenylalanine
Tryptophan
Tyrosine

NOTE: you are not expected to know the chemical structures of the amino acids but you should
know which ones are in each category and why.

Peptide Bonds
Background textbook reading:
 Section 4.1 Molecular Structure of Proteins (pp.
73-74)

The formation of the peptide bond involves the release of

a water molecule. The carboxyl group of one amino acid
reacts with the amino group of the adjacent amino acid.
The C=O group in the peptide bond is the carbonyl group
and the N-H group is the amide group. Label these in the
diagram on the right.
Notice that the R-groups of each amino acid in the
peptide point in a different direction.
In the polypeptide, the ends are chemically distinct. One
end is the amino end and the other is the carboxyl end.

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Polypeptides are typically long in length. In humans, the shortest are about 100 amino acids long
while the longest is 34,350 amino acids long.

Polypeptide or protein what’s the difference?

The terms are used interchangeably. More accurately the term protein refers to a polypeptide
chain that’s has been folded into a stable, three-dimensional structure
Polypeptide is a chain and a protein is polypeptides that have been folded up

Levels of Protein Structure

Background textbook reading:
 Section 4.1 Molecular Structure of Proteins (pp. 73-79)

The sequence of amino acids is just the first of many levels of protein structure.

Primary structure is like “beads

on a string”

Secondary structure is like the

first level of basic folding

Tertiary structure defines a

more 3-dimensional shape and
determines function

Quaternary structure is when

two or more polypeptide chains
made up subunits that come
together in a more complex
structure

Primary structure is simply the sequence of amino acids in a protein.

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Secondary structure results from hydrogen bonds and causes localized folding of the polypeptide
chain. Between which groups do the hydrogen bonds form?
Hydrogen bonds can form between the CARBONYL GROUP of one peptide bond and the AMIDE GROUP in
another. This allows for folding

There are two types of secondary structure:

Alpha (α) helix: Beta (β) sheet:

From studying the diagrams above, you should see that the hydrogen bonds form between the
same groups in the alpha helix and the beta sheet. If the same groups are involved, then why are
there two different structures that result? First amino acid and then four ahead between carbonyl
group and amid

There are two different structures because in helices the helix is stabilized by hydrogen bonds that form between each amin

Tertiary Structure:
This refers to the three-dimensional structure of a single polypeptide chain and determines the
function of the protein. Tertiary structure is determined mainly by interactions between the R
groups. How is this different than secondary structure?

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Tertiary structure is determined by the spatial distribution of hydrophilic and hydrophobic R groups along
the molecule, as well as by different types of chemical bonds and interactions that form between various R
groups ->
More specifically, tertiary structure is determined by the positioning of the R groups along the
molecule and the types of interactions between the different R groups. Tertiary structure often
includes looping and folding of the polypeptide that allow the R groups to be in closer proximity so
the bonds can form. Tertiary structure can be shown in different ways as seen below (a. ball-and-
stick model; b. ribbon model; c. space-filling model)

Quaternary structure
Many proteins are complete and functional at the level of tertiary structure but some proteins are
made up of two or more subunits that are bound together forming the next level of structure
called quaternary structure. The activity of a protein with multiple subunits depends on the
quaternary structure that forms from the combination of the tertiary structures. The subunits of a
protein with quaternary structure may be identical (such as in ‘a’ below, an HIV protein) or
different (such as in ‘b’ below, hemoglobin).

Protein folding (proteins ‘helping’ proteins)

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Most proteins (75%) fold into their final conformation within milliseconds of being synthesized.
Other proteins fold more slowly and as such, their hydrophobic groups are exposed to other
macromolecules in the cytoplasm. This along with the hydrophobic effect and van der Waals
interactions can prevent proper folding. In addition, proteins that have already folded may become
denatured and so experience the same cytoplasmic environment as proteins that fold slowly.
Cells have evolved protective proteins called chaperones. These proteins protect slow-folding
proteins or denatured proteins by binding with the hydrophobic and non-polar R groups and
shielding them from aggregating. Chaperones bind and release a polypeptide in repeated cycles
giving the polypeptide time to attain its proper shape.

Extra note
Which of the following DNA molecules would be more stable under conditions of increasing
temperature?
A DNA molecule that has more guanine and cytosine nucleotides. Because between guanine and cytosine
there are 3 hydrogen bond keeping them together (2 in A and T) these 3 H bonds make DNA stronger.