proteins

Proteins are polymers (polypeptides) of what?

Amino acids (AA’s)

How many mammalian amino acids are there?

20

Are mammalian amino acids in the D or L configuration?

L-configuration

What do all proteins contain in their molecular structure?

1. Amino group

2. Carboxylate group bound to a central alpha carbon

3. A distinct side chain “R” (a different one for each AA)

In a protein, is the carboxylate group a weak or strong acid?

Weak acid

What charge does the carboxylate group in a protein carry at physiologic pH?

A negative charge

In a protein, is the amine group a weak or strong base?

Weak base

In a protein, what charge does the amine group carry?

Positive charge

What is the overall charge of a protein?

Neutral

What effect do the combined properties of a protein produce?

A buffering effect

What happens to amino acids in an acidic environment?

They become positively charged

What happens to amino acids in a base environment?

An overall negative charge occurs

What does the pKa of an individual amino acid determine?

Their charge at various pH values (depending on the side chain structure).

Will different R group side chains of an amino acids have differing chemical properties and sometimes charges?

Yes

Amino Acids with Electrically Charged Side Chains:

What are 3 amino acids with charged side chains that have a positive charge at physiologic pH and act as a BASE?

1. Arginine

2. Histidine

3. Lysine

Amino Acids with Electrically Charged Side Chains:

What are 2 amino acids with charged side chains that tend to have a negative charge at physiologic pH and act as an ACID?

1. Aspartate

2. Glutamate

Amino Acids with Electrically Charged Side Chains:

What kind of bonding can all amino acids with charged side chains participate in?

Hydrogen bonding

Amino Acids with Electrically Charged Side Chains:

Which amino acids with charged side chains can participate in ionic bonds?

Lysine and arginine

Amino Acids with Electrically Charged Side Chains:

Charged side chains are just one of several properties that can alter what of a protein/polypeptide?

The ultimate shape and function

Amino Acids with Electrically Charged Side Chains:

Are amino acids with charged side chains hydrophobic or hydrophilic?

Hydrophilic

Amino Acids with Hydrophobic Side Chains:

What shape are aliphatic side groups?

Small open carbon chains (not rings)

Amino Acids with Hydrophobic Side Chains:

Do aliphatic side groups participate in hydrogen bonding?

No

Amino Acids with Hydrophobic Side Chains:

What shape are aromatic side groups?

Bulky hydrophobic rings

Amino Acids with Hydrophobic Side Chains:

What do hydrophobic side groups tend to do with each other?

Group together away from the aqueous environment surrounding the protein molecule

Amino Acids with Polar Uncharged Side Chains:

Do amino acids with polar uncharged side groups participate in hydrogen bonding?

Yes

Amino Acids with Polar Uncharged Side Chains:

Are amino acids with polar uncharged side groups hydrophilic or hydrophobic?

Hydrophilic

Amino Acid Special Cases:

Cysteine can form what kind of bonds with other cysteine molecules?

Disulfide bonds in the same or different polypeptide strand

Amino Acid Special Cases:

What makes glycine unusual?

Its side chain is simply a hydrogen atom and has a small footprint

Amino Acid Special Cases:

What kind of side group does proline contain?

A nitrogen containing ring

Amino Acid Special Cases:

What does the shape of proline’s side group contribute to?

The ring shape contributes a kink in the peptide chain (often found in sharp bends of the protein molecule)

Overall, what determines the properties and function of a protein?

The 3D conformation

What are the 4 degrees of structure that contribute to the shape of a protein?

1. Primary

2. Secondary

3. Tertiary

4. Quaternary

What are the 4 degrees of structure that contribute to the shape of a protein?

1. Primary

2. Secondary

3. Tertiary

4. Quaternary

When one amino acids bonds to another, what kind of bond is formed?

A peptide bond

What do peptide bonds result in?

A chain of subunits that is described as having an N-terminus and a C-terminus

What is the N-terminus and the C-terminus

N-terminus = terminal amino side of one AA

C-terminus = terminal carboxylate group of another AA

In the primary structure the carboxylate (carboxylic acid) group of one amino acid bonds with what?

The amine group of another AA

What bonds form the amide functional group?

Peptide bonds

The sequence of amino acids is not only important for shape of the protein but also for what? (3 things)

1. Enzyme binding site characteristics

2. Flexibility OR rigidity necessary for functions

3. Folding and conformation of the protein

Why is the primary structure of a protein so important? (Think big picture)

Even one error of substitution in the AA sequence can have drastic consequences for the overall shape/function of the protein

What’s an example of a disorder resulting from a single amino acid substitution (in the hemoglobin protein)?

Sickle cell anemia

During sickle cell, which AA is substituted?

The glutamate (glutamic acid) is substituted for valine

In sickle cell, why is the substitution for glutamate (glutamic acid) with valine bad?

Valine has a hydrophobic alpha carbon side chain that changes the overall shape of the protein strand. The strand becomes linear and deforms the shape of RBCs (leading to hemolysis and organ damage)

What are secondary structures of proteins?

Regions of recurring, localized shapes

What are the secondary structures of proteins produced by?

produced from interaction of amino acids in response to each other and their environment

What are 2 examples of secondary structures?

1. Alpha helix

2. Beta pleated sheet

Which secondary structure is considered “common, rigid, and stable”?

The alpha helix

What results in the formation of the alpha helix?

Results from hydrogen bonding between the carboxyl group of one AA and the amino group of another AA that is located 4 bonds down the chain

The beta pleated sheet is common and results from maximized hydrogen bonding but tends to be an interaction between what?

Neighboring parallel polypeptide strands (may or may not be the same polypeptide)

The “pleated” conformation of the beta pleated sheet is great for optimizing what?

The hydrogen bonding between amino and carboxyl groups

It needs to be noted that secondary structure is the result of _____ and NOT ______

Secondary structure is the result of hydrogen bonding between the amino and carboxylate groups of then AAs in the structure and NOT the different R groups on each amino acid

The R groups are important in determining what?

Tertiary structure

Is secondary structure very LOCAL on the polypeptide?

Yes. Nearby amino acids are interacting via hydrogen bonding

Which structure level tends to be repetitive and sometimes gives form to large parts of a polypeptide?

The secondary structure

What are the non-repetitive secondary structures?

Bends, loops, and turns

How are protein structures often depicted?

As ribbon drawings using coils for alpha helices and arrows for beta pleated sheets

What are tertiary structures the result of?

Interactions between secondary structures of the polypeptide, producing the ultimate 3D conformation

The 3D structure of a protein is dynamic and flexible. What does this allow for?

Allows for functional conformational changes as its environment dictates

What are structural domains?

Distinct regions of structure that are usually connected via simpler features such as loops

What kind of proteins have structural domains?

Fully formed proteins

What structural component do globular proteins have?

Folds

What do the folds of globular proteins act as?

Binding sites for molecules such as ATP

What does the hydrolysis of ATP result in as it relates to this lecture?

The closure of folds in globular proteins which changes the 3D configuration of the structure

What are examples of transmembrane proteins structures?

Ion channels, transport proteins, neurotransmitter receptors and hormone receptors

Many transmembrane proteins contain similar structures such as what?

Alpha helices with hydrophobic AA residues

What are quaternary structures?

The integration of separate polypeptides into a larger functional unit

What are the 4 types of quaternary structure?

Dimers

Trimers

Tetramers

Oligomers

Quaternary structure can also be referred to as homo or hetero for what reason?

To indicate whether subunits that are linking together are the same or different

What are the forces responsible for quaternary structures?

• hydrogen bonding

• Association of nonpolar side chains

• Occasionally ionic bonds or “salt bridges”

Are quaternary structures ever held together by covalent bonds?

No

Are quaternary bonds frequently or rarely held together by disulfide bonds?

Rarely

Hemoglobin is a classic example of which level of structure?

Quaternary structure

What subunits is hemoglobin composed of?

It is a tetramer composed of:

• 2 alpha polypeptides

• 2 beta polypeptides

What is one of the rare examples of a quaternary structure resulting from a disulfide bond?

Immunoglobulins (antibodies)

What structure ultimately determines how proteins fold into their final conformation?

Primary structure

What does “native conformation” of a polypeptide mean?

A protein can assume various shapes HOWEVER when given the same environment the same protein will assume the same shape

What can help proteins to achieve their native functional conformation?

Enzymes or other proteins

Is it easy or difficult to predict the actual shape of a polypeptide from it amino acid sequence?

Difficult (AI is starting to help us with this)

What is a denatured protein?

One that has lost it tertiary and/or secondary structure

What can cause a protein to become denatured?

• Changes in temperature, pH, and solvent the protein is in

• Modification of individual amino acids through oxidation or glycosylation

What happens to proteins in an acidic environment?

The ionic and hydrogen bonds of carboxylic acids loses its charge (O- becomes OH)

What happens to proteins in a base environment?

Ionic and hydrogen bonds of basic amino acids becomes disrupted (RNH3+ becomes RNH2)

What is one of the many reasons why its important for our bodies to require a tight control of acid/base balance and temperature?

Because ultimately the functional shape of a protein is highly dependent on specific physiologic factors

What are variant regions of amino acids composition?

Regions of composition where if there are variations, it is non-critical

Example: polymorphism

What are invariant regions of amino acid composition?

Regions of composition that are critical for function, structure and binding sites

What do invariant regions need to properly function?

The exact same amino acid sequence

What are protein families and superfamilies?

Homologous groups of proteins in the body that are related to an ancestral protein

What are paralogs? And give an example

Myoglobin and hemoglobin are examples. They are similar proteins with related but different functions

What exactly is myoglobin?

An intracellular heme protein that functions to store and transport oxygen to mitochondria

What is myoglobin presumed to have evolved from?

The alpha chain genetic code of hemoglobin

What are isoforms (isoenzymes)?

Different versions of the same protein that vary based on tissue type and developmental stage

What is translation?

The process of protein synthesis from RNA instructions

When does translation occur?

Usually after full synthesis and 3D conformation

Why are modifications made to specific amino acids?

To regulate function, anchor proteins to membranes, and enhance a proteins association with other functional proteins

What is glycosylation?

A type of protein modification where oligosaccharides are bonded to O or N of certain amino acids

AKA “carbohydrate flagging” for cell recognition and signaling

What is fatty acylation?

A protein modification where there is an addition of a fatty acid to the lipid membranes and intracellular vesicles where they interact hydrophobically with other lipid membranes

What are 3 examples of regulatory modifications? (Functions that “fine-tune protein activity)

1. Phosphorylation - adds phosphate groups (turns proteins on or off)

2. Acetylation - changes protein activity

3. ADP-ribosylation - regulates function