Protein Tertiary Structure Flashcards
How Proteins Fold:
Proteins are composed of amino acids.
Amino acids are linked by peptide bonds to form the primary structure of a protein.
There are 20 different amino acids, each with
unique side chains.
The sequence of amino acids and the chemistry of the side chains determines how the protein folds which, in turn, determines the protein structure and function.
There are four types of bonds found in
Tertiary and Quaternary structures:
- Disulfide bridges
- Salt bridges
- Hydrogen bonding
- Hydrophobic interactions
It is important to realize that all four…
forces can be used for a protein to function in its specific role.
- If any or all of these forces are changed, the protein’s nature is also changed.
- The protein is then said to be denatured.
Secondary structure of a protein is the…
arrangement of the polypeptide backbone of the protein in space.
Secondary structure includes…
two kinds of repeating patterns: a-helix and b-sheet.
(Secondary structure) Hydrogen bonding between backbone
atoms are…
responsible for both of these
secondary structures.
Tertiary Protein Structure:
The overall three dimensional shape that results from the folding of a protein chain.
Tertiary structure depends mainly on…
attractions of amino acid side chains that are far apart along the same backbone.
Non-covalent interactions…
and disulfide covalent bonds govern tertiary structure.
native state:
The shape in which a protein exists naturally in a living organism.
Quaternary Protein Structure:
The way in which two or more polypeptide subunits associate to form a single threedimensional protein unit.
- Non-covalent forces are responsible for
quaternary structure essential to the
function of proteins.
Protein Denaturation:
The loss of secondary, tertiary, or quaternary
protein structure due to disruption of noncovalent interactions and or disulfide bonds
BUT that leaves peptide bonds and primary
structure intact.
Agents that causes denaturation:
Heat, Mechanical agitation, detergents, organic compounds, pH change, and inorganic salts.
Heat Agent:
The weak side-chain attractions in
globular proteins are easily broken by heating. -e.g. cooking meat converts some of the insoluble collagens into soluble gelatin.
Mechanical Agitation Agent:
- Most familiar example of denaturation of protein by mechanical agitation is the foaming that occurs during beating of egg whites.
Detergents Agent:
Very low concentrations of
detergents can cause denaturation by disrupting the association of hydrophobic side chains.
Organic compounds Agents;
Polar solvents such as acetone or ethanol can interfere with hydrogen bonding by competing for bonding sites.
pH change Agents:
- Excess H+
or OHions reacts
with the basic or acidic side chains in amino
acid residues and disrupts salt bridges.
Inorganic salts Agents
- Sufficiently high
concentrations of ions can disrupt salt bridges
How does the unfolded protein adopt the
native state?
This has proven to be a very challenging
problem. It has been described as the
second half of the genetic code, or as the
3-dimensional code, as opposed to the
1-dimensional code of the nucleotide/amino
acid sequence.
-Predict 3D structure from primary
sequence
– Avoid misfolding related to human
diseases
– Design proteins with novel functions
Anfinsen
Experiment
Denaturation of
ribunuclease A
(4 disulfide bonds) with
8 M Urea containing
b-mercaptoethanol to form
a random coil with no
activity
Urea – denatures
b-MeSH – reduces Cy
After renaturation…
the refolded protein has native activity
despite the fact that there are 105 ways to renature the
protein.
Conclusion: All the information necessary for folding the
peptide chain into its native structure is contained in the
primary amino acid sequence of the peptide.
Anfinsen Experiment: Remove b-mercaptoethanol only
oxidation of the sulfhydryl group, then
remove urea → scrambled protein, no
activity
- Further addition of trace amounts of b- mercaptoethanol converts the
scrambled form into native form. - Conclusion: The native form of a protein
has the thermodynamically most stable
structure.
Quick Review: Tertiary Structure
*Specific overall shape of a protein
- Cross links between R groups of amino acids in
chain
Disulphide
ionic
H bonds
hydrophobic
Globular and Fibrous Proteins:
Globular proteins
“spherical” shape
Fibrous proteins
long, thin fibers
Quaternary Structure
-Proteins with two or more chains
- Example is hemoglobin
Carries oxygen in blood
Four polypeptide chains
Each chain has an iron-containing
heme group to bind oxygen
