Chapter 3 Proteins I: An Introduction to Protein Structure and Function
1. Protein function is determined by protein structure—what level of protein structure do
you think is most important? The tertiary structure
3.3. Proteins Are Molecules of Defined Shape and Structure
2. What is the primary level of structure of a polypeptide or protein? primary
- Would you predict changes in the primary sequence of a protein would affect its
function? Do you think all changes would have the same effect? Explain: yes,
changes to the primary sequence would affect protein function, but not all would
be super extreme. For example Conservative substitution (changing a
hydrophobic a.a for a similar one) usually has no observed difference in protein
structure/function. Vs a radical substitution (for example a bulky hydrophobic
a.a for a small negatively charged amino acid) could result in change in
conformation/function.
- Changes to a appearance/properties of a protein could be the result of changes
to the #, type, and positions and order of a.as
3. Protein Secondary (2°) Structures: α Helices
- Describe the alpha (α) helix in terms of overall structure, role of peptide bonds
and other bonds (dihedrals), position of side chains, and chemical interactions
that stabilize it—what parts are involved in hydrogen bonding? The alpha helix is
formed with peptide bonds (w/right hand spiral). This is held together by the LP
electrons on the carbonyl oxygens with form H-bonds w/peptide nitrogens 4
a.as in front of it.
- How do alanine (Ala) and leucine (Leu) affect α helix formation? What about
glycine (Gly) or proline (Pro)? Gly: has a SMALL side chain (H atom) it is floppy
and does not favour the helix formation (leads to kinks or termination of helix at
Pro). Pro: lacks protons needed for H-bonding – destabilizing the helix. Ala: side
chain is CH3 (not bulky) and limits unfav ints. Leu stabalize helixes can intimacy
w/other hydrophobic side chains in a helical structure.
4. Protein Secondary Structures: β Sheets
- Describe β sheets (structures & bonds), and distinguish between parallel and
antiparallel configurations.
- B sheets: formed by H-bonds b/w carbonyl oxygens and the peptide hydrogen +
nitrogens. a.a side chains attached to backbone alt on each side of the sheet
(perpendicular to plane created by backbones)
- Parallel: strands in same direction (rectangular pattern of H-bonding
- Antiparallel: opp directions of strands (Trapezoidal shape)
5. Protein Tertiary (3°) Structures
- What is a motif? Can you give some examples of motifs found in protein
structure? Combinations of secondary structure can be part of a domain (but not
a domain). It is a short conserved sequence pattern associated with distinct
functions of a protein or DNA.
, - Alpha motifs: helix-turn-helix, three-helic bundle, four-helix bundle, and the
globin fold (has at least 8 helices - more complex)
- Beta motifs: Greek-key motif ( 4 strands of b sheet); B barrel (B sheet that has
been closed to form a barrel struck); B propeller (B sheet that is twisted from
center point to look like a propeller); immunoglobulin fold (has flattened B barrel
structure - more complex)
- Which forces are more important in stabilizing protein structures: covalent or
noncovalent? Noncovalent (weak)
- Which covalent forces stabilize proteins? disulfide bonds
- Which noncovalent forces stabilize proteins? van der waals, cation
pi-ints, salt bridges, and H-bonding
6. How are Protein Quaternary (4°) Structures different from Tertiary Structures?
They have all the same bonds however this is usually how we find proteins. They are
multiple subunits (i.e. tertiary structures) bonded together
7. Explain the forces involved in stabilizing all four levels of protein structure (1°-4°). What
kinds of molecular forces are involved? What kinds of chemical bonds are involved?
- Primary: linear a.a linking by covalent peptide bonds (formed between the
amino group of one amino acid and the carboxyl group of another) & disulfide
bonds (in some proteins)
- Secondary: H-bonds (b/w carbonyl oxygen of one a.a +the amide hydrogen of
another = primary stabilizing force) dipole interactions (align + stabilize)
- Tertiary: molecular forces= hydrophobic ints (non polar side chain driven
together by the hydrophobic effect), H-bonds (b/w side chains + backbone),
Ionic bonds (electrostatic ints b/w opp charged side chains – form salt bridges –
STABALIZE), Van der waals (close range attractions), and disulfide bridges
(b/w cys residues = STRONG w/in or b/w polypep chains = INC STABILITY)
3.4. Examples of Protein Structures and Functions
8. This is an introduction and general overview of protein structure/function relationships.
Look at the overall structure of each of the following proteins—try to find their most
distinguishing features at the different levels of structure:
- Can you identify secondary structures in each of the proteins?
- Can you classify each protein as a fibrous protein or a globular protein (or even a
combination)?
- Identify which proteins have a quaternary structure. Do any have prosthetic or
accessory groups?
9. Aquaporin: secondary structure= 4 subunits each made of 6 transmembrane alpha
helices; fibrous protein or a globular protein: Neither, integral transmembrane
quaternary structure? 4 subunit prosthetic or accessory groups? no
- What is the primary function of aquaporins? To act as pores in membrane
allowing h2o in/out
- Where are aquaporins found? In the lipid bilayer of plasma membrane
- How do their specific structures aid in their functioning? They have 6
transmembrane alpha helices creating a bundle – where h20 passes through
, 10.Chymotrypsin: secondary structure= 2 compressed beta barrels and 1 short alpha
helix; fibrous protein or a globular protein: Globular quaternary structure?
prosthetic or accessory groups? No
- What is the primary function of chymotrypsin? an enzyme produced by pancreas
and secreted into intestinal lumen. - it cleaves dietary proteins into peptides
- If only three active-site amino acids are directly involved in the catalytic
function of chymotrypsin, why does the protein contain at least two
hundred other amino acids? The other amino acids are for recognition
and binding of protein being cleaved
11.Collagen: secondary structure=Collagen helix: composed of glycine, proline, and
hydroxyproline. But not alpha helical = collagen helix (3 helical filaments wrapped
around each other) fibrous protein or a globular protein: Fibrous; quaternary
structure? Bundles or triple helices; prosthetic or accessory groups? No
- Look carefully at the structure of collagen—how is a collagen triple-helix different
from the alpha-helices found in other proteins? Helical filaments twist around
each other – doesn’t create an alpha helix, its left handed and less compact
- What kinds of forces and interactions stabilize collagen? H-bonds, hydrophobic
ints, covalent bonds (cross links), electrostatic (ionic) ints, proline and
hydroxyproline rigid
- How is the structure of collagen critical for its biological function? Due to its
rigidity and resistance to stretching, it is the perfect matrix for skin, tendons,
bones, and ligaments
- Describe the special post-translational modification required for both structure
and function of collagen fibres: hydroxyproline is a modified a.a by prolyl
hydroxylase (an enzyme). The enzyme uses oxygen to complete mold and
requires ascorbate (vitamin C) to reduce enzyme back to active form. prolyl
hydroxylase cannot function properly is absence of ascorbate (hydroxylation
cannot occur), this leads to lack of -OH groups on collagen and loss of structure
and can lead to scurvy, weakened connective tissue, bleeding, and tooth loss
12.Hemoglobin: secondary structure= Tetrameric molecule: 2 alpha chains and 2 beta
chains. Each with a heme functional group. Mostly alpha helices joined by turns. fibrous
protein or a globular protein:Globular; quaternary structure? Tetrameric (4 subunits);
prosthetic or accessory groups? Heme
- Describe the overall structure of hemoglobin in terms of the numbers and kinds
of subunits, and any accessory groups: its is a tetrameric (4 subunit) protein,
that has 8 alpha helices connected by turns – or may have 2 alpha chains and 2
beta chains
- The primary function of hemoglobin is to transport oxygen from the lungs to
tissues—how many oxygen molecules can one hemoglobin carry, and where do
oxygen molecules bind to hemoglobin? In each of the subunits of hemoglobin
1. Protein function is determined by protein structure—what level of protein structure do
you think is most important? The tertiary structure
3.3. Proteins Are Molecules of Defined Shape and Structure
2. What is the primary level of structure of a polypeptide or protein? primary
- Would you predict changes in the primary sequence of a protein would affect its
function? Do you think all changes would have the same effect? Explain: yes,
changes to the primary sequence would affect protein function, but not all would
be super extreme. For example Conservative substitution (changing a
hydrophobic a.a for a similar one) usually has no observed difference in protein
structure/function. Vs a radical substitution (for example a bulky hydrophobic
a.a for a small negatively charged amino acid) could result in change in
conformation/function.
- Changes to a appearance/properties of a protein could be the result of changes
to the #, type, and positions and order of a.as
3. Protein Secondary (2°) Structures: α Helices
- Describe the alpha (α) helix in terms of overall structure, role of peptide bonds
and other bonds (dihedrals), position of side chains, and chemical interactions
that stabilize it—what parts are involved in hydrogen bonding? The alpha helix is
formed with peptide bonds (w/right hand spiral). This is held together by the LP
electrons on the carbonyl oxygens with form H-bonds w/peptide nitrogens 4
a.as in front of it.
- How do alanine (Ala) and leucine (Leu) affect α helix formation? What about
glycine (Gly) or proline (Pro)? Gly: has a SMALL side chain (H atom) it is floppy
and does not favour the helix formation (leads to kinks or termination of helix at
Pro). Pro: lacks protons needed for H-bonding – destabilizing the helix. Ala: side
chain is CH3 (not bulky) and limits unfav ints. Leu stabalize helixes can intimacy
w/other hydrophobic side chains in a helical structure.
4. Protein Secondary Structures: β Sheets
- Describe β sheets (structures & bonds), and distinguish between parallel and
antiparallel configurations.
- B sheets: formed by H-bonds b/w carbonyl oxygens and the peptide hydrogen +
nitrogens. a.a side chains attached to backbone alt on each side of the sheet
(perpendicular to plane created by backbones)
- Parallel: strands in same direction (rectangular pattern of H-bonding
- Antiparallel: opp directions of strands (Trapezoidal shape)
5. Protein Tertiary (3°) Structures
- What is a motif? Can you give some examples of motifs found in protein
structure? Combinations of secondary structure can be part of a domain (but not
a domain). It is a short conserved sequence pattern associated with distinct
functions of a protein or DNA.
, - Alpha motifs: helix-turn-helix, three-helic bundle, four-helix bundle, and the
globin fold (has at least 8 helices - more complex)
- Beta motifs: Greek-key motif ( 4 strands of b sheet); B barrel (B sheet that has
been closed to form a barrel struck); B propeller (B sheet that is twisted from
center point to look like a propeller); immunoglobulin fold (has flattened B barrel
structure - more complex)
- Which forces are more important in stabilizing protein structures: covalent or
noncovalent? Noncovalent (weak)
- Which covalent forces stabilize proteins? disulfide bonds
- Which noncovalent forces stabilize proteins? van der waals, cation
pi-ints, salt bridges, and H-bonding
6. How are Protein Quaternary (4°) Structures different from Tertiary Structures?
They have all the same bonds however this is usually how we find proteins. They are
multiple subunits (i.e. tertiary structures) bonded together
7. Explain the forces involved in stabilizing all four levels of protein structure (1°-4°). What
kinds of molecular forces are involved? What kinds of chemical bonds are involved?
- Primary: linear a.a linking by covalent peptide bonds (formed between the
amino group of one amino acid and the carboxyl group of another) & disulfide
bonds (in some proteins)
- Secondary: H-bonds (b/w carbonyl oxygen of one a.a +the amide hydrogen of
another = primary stabilizing force) dipole interactions (align + stabilize)
- Tertiary: molecular forces= hydrophobic ints (non polar side chain driven
together by the hydrophobic effect), H-bonds (b/w side chains + backbone),
Ionic bonds (electrostatic ints b/w opp charged side chains – form salt bridges –
STABALIZE), Van der waals (close range attractions), and disulfide bridges
(b/w cys residues = STRONG w/in or b/w polypep chains = INC STABILITY)
3.4. Examples of Protein Structures and Functions
8. This is an introduction and general overview of protein structure/function relationships.
Look at the overall structure of each of the following proteins—try to find their most
distinguishing features at the different levels of structure:
- Can you identify secondary structures in each of the proteins?
- Can you classify each protein as a fibrous protein or a globular protein (or even a
combination)?
- Identify which proteins have a quaternary structure. Do any have prosthetic or
accessory groups?
9. Aquaporin: secondary structure= 4 subunits each made of 6 transmembrane alpha
helices; fibrous protein or a globular protein: Neither, integral transmembrane
quaternary structure? 4 subunit prosthetic or accessory groups? no
- What is the primary function of aquaporins? To act as pores in membrane
allowing h2o in/out
- Where are aquaporins found? In the lipid bilayer of plasma membrane
- How do their specific structures aid in their functioning? They have 6
transmembrane alpha helices creating a bundle – where h20 passes through
, 10.Chymotrypsin: secondary structure= 2 compressed beta barrels and 1 short alpha
helix; fibrous protein or a globular protein: Globular quaternary structure?
prosthetic or accessory groups? No
- What is the primary function of chymotrypsin? an enzyme produced by pancreas
and secreted into intestinal lumen. - it cleaves dietary proteins into peptides
- If only three active-site amino acids are directly involved in the catalytic
function of chymotrypsin, why does the protein contain at least two
hundred other amino acids? The other amino acids are for recognition
and binding of protein being cleaved
11.Collagen: secondary structure=Collagen helix: composed of glycine, proline, and
hydroxyproline. But not alpha helical = collagen helix (3 helical filaments wrapped
around each other) fibrous protein or a globular protein: Fibrous; quaternary
structure? Bundles or triple helices; prosthetic or accessory groups? No
- Look carefully at the structure of collagen—how is a collagen triple-helix different
from the alpha-helices found in other proteins? Helical filaments twist around
each other – doesn’t create an alpha helix, its left handed and less compact
- What kinds of forces and interactions stabilize collagen? H-bonds, hydrophobic
ints, covalent bonds (cross links), electrostatic (ionic) ints, proline and
hydroxyproline rigid
- How is the structure of collagen critical for its biological function? Due to its
rigidity and resistance to stretching, it is the perfect matrix for skin, tendons,
bones, and ligaments
- Describe the special post-translational modification required for both structure
and function of collagen fibres: hydroxyproline is a modified a.a by prolyl
hydroxylase (an enzyme). The enzyme uses oxygen to complete mold and
requires ascorbate (vitamin C) to reduce enzyme back to active form. prolyl
hydroxylase cannot function properly is absence of ascorbate (hydroxylation
cannot occur), this leads to lack of -OH groups on collagen and loss of structure
and can lead to scurvy, weakened connective tissue, bleeding, and tooth loss
12.Hemoglobin: secondary structure= Tetrameric molecule: 2 alpha chains and 2 beta
chains. Each with a heme functional group. Mostly alpha helices joined by turns. fibrous
protein or a globular protein:Globular; quaternary structure? Tetrameric (4 subunits);
prosthetic or accessory groups? Heme
- Describe the overall structure of hemoglobin in terms of the numbers and kinds
of subunits, and any accessory groups: its is a tetrameric (4 subunit) protein,
that has 8 alpha helices connected by turns – or may have 2 alpha chains and 2
beta chains
- The primary function of hemoglobin is to transport oxygen from the lungs to
tissues—how many oxygen molecules can one hemoglobin carry, and where do
oxygen molecules bind to hemoglobin? In each of the subunits of hemoglobin
