Perspective:

Scale of the Cellular World

Object

Real Size

X 106

Water
Alanine
Diam. DNA
Hemoglobin
Ribosome
Polio Virus
Mitochondrion
E. coli
Liver cell

0.28 nm
0.5 nm
2.5 nm
7.0 nm
20 nm
30 nm
1500 nm
2000 nm
20,000 nm

0.28 mm
0.5 mm
2.5 mm
7 mm
2 cm
3 cm
1.5 m
2m
20 m

pH
pH is a measure of the acidity or basicity of an
aqueous solution
pH ~ -log[H+]
pH>7 is basic
pH<7 is acidic
pH influences most biological processes and is
usually near 7 (neutral) in living cells

Reflection
Can you think of an
example in your body
where the pH is not
neutral (i.e., near pH
7)??

Non-covalent bonding
in biological systems
Hydrogen bonds
Shared hydrogen between two molecules or parts
of a molecule

Non-covalent bonding
in biological systems
Ionic/electrostatic interactions

Non-covalent bonding
in biological systems
Hydrophobic interactions/forces

Non-covalent bonding
in biological systems
van der Waals Interactions

Fig. Geckos climb on sheer

surfaces using van der Waals
forces between the surface
and microscopic projections
on their footpads

IMPORTANT:
Approximate Bond Strengths

Non-covalent Bonding Essential to Life

Promotes assembly
Occurs spontaneously
Driven by interaction energy
Large number of small forces creates flexibility of
structures
Example: Membranes/lipid bilayer

Reflection
Why are the
properties of
water so
essential to life
as we know it?

Proteins Composed of Amino Acids

Order of amino acids determined by
nucleotide sequence in DNA
Corollary Proteins are manifestation of
DNA sequence
Intermediary process to copy DNA
(transcription) and assemble amino acids
(translation)
More on these processes later in semester

Bottom line: DNA sequence linked to RNA

sequence linked to protein sequence

Amino Acid Structure

Properties of Side Chains Important

Multiple types
Acidic (glutamic acid, Glu, E)
Basic (lysine, Lys, K)
Polar (serine, Ser, S)
Apolar/hydrophobic (tryptophan, Trp, W)
H (glycine, Gly, G)
Know these properties of the side chains!!
Assigned one structure in each category to be
able to recognize

Properties of Side Chains Important

Multiple types
Acidic (glutamic acid, Glu, E)
Basic (lysine, Lys, K)
Polar (serine, Ser, S)
Apolar/hydrophobic (tryptophan, Trp, W)
H (glycine, Gly, G)

Game (Lame Game??):

Link to the game

Amino
Acid
Structures

Proline
Only imino acid:

Amino
Acid
Structures
Annotated

Reflection
Why are the
properties of the
amino acid side
chains
important?

PROTEIN STRUCTURE

Proteins are polymers assembled from amino

acids units (IMPORTANT)
Only 20 natural amino acids make up many 1000s
of proteins
Linked by peptide bonds to form a polymer
Structure designated in two different ways
Peptide bonds and amino acid core form the backbone
Each amino acid provides a unique side chain

PROTEIN STRUCTURE
Proteins are written from N-terminus to Cterminus aa sequence is PRIMARY STRUCTURE
Actually synthesized in that orientation
Always written in this orientation
Often written as a sequence of 1- or 3-letter
abbreviations: GKPEESWEG
GlyLysProGluGluSerTrpGluGly

Patterns of Protein Structure

In the 1930s William Astbury studied
wool and hair using X-ray fiber diffraction
(similar to DNA studies)
Data showed coiled molecular structure
that he called alpha (later to become ahelix)
When heated or stretched, another pattern
was observed that he called beta (later to
become b-structure or b-sheet)

Alpha Helical Structure

Identified by Pauling
Historic Article

Link to YouTube video about alpha helix

Alpha Helical Structure

Backbone hydrogen
bonding between
amino and carbonyl
separated by 4
residues

Link to YouTube video about alpha helix

Alpha Helical Structure

Backbone hydrogen
bonding within the
same strand

Link to YouTube video about alpha helix

Alpha Helical Structure

Can have interactions
of R groups (not shown
here in poly-Ala) to
stabilize helix

Link to YouTube video about alpha helix

Beta-Sheet Structure
Backbone hydrogen bonding
between strands

Link to YouTube video about beta sheets

Beta-Sheet Structure
Backbone hydrogen bonding
between strands
Note interaction between R
groups (does this limit R size?)

b-Sheet Structure
Orientation can be
anti-parallel
or
parallel

BetaSheet
Structure

Reflection
Why do you think that
the a-helix and b-sheet
are each referenced as
secondary structure?
How does the energy of
these structures compare
to the energy of the
peptide bond?

Reflection
What contribution does
the side chain of each
amino acid make to
secondary structure?
Would you expect all
amino acids participate
in secondary structure?

Levels of Protein Structure

Primary Structure: Amino acid sequence
Secondary Structure:
a-helix/b-sheet

Tertiary Structure:
Folding into 3-dimensions

Quaternary Structure:
Assembly into higher oligomers

PROTEIN FOLDING
Amino acid sequence of a protein
not functional without folding
3-D structure is the active form of a protein
Non-covalent bonds between side chains (and
peptide backbone interactions) create the
folded form of the protein (IMPORTANT)
Folded form exhibits a biological activity
Folding of amino acid sequence based on
DNA sequence is path to FUNCTION!

Bonds Utilized in Protein Folding

Disulfide
bond
formation
(covalent
bond) can
stabilize
protein fold

Stabilizing energy for protein folding:

Primarily non-covalent interactions

Bringing Alpha Helices/Beta Sheets

Together in a Folded Structure
Interactions occur rapidly and result in the folded structure
Process is dynamic

AND

Structure is dynamic

Link to YouTube video about protein folding

Link to another YouTube video about protein folding

Protein Folding Funnels

Energetic Pathways to Function

Protein Folding Funnels

Energetic Pathways to Function

Large energy penalty for loss of entropy think of it as loss of options for
different states so that the overall difference in energy between
folded/unfolded is small!

Protein Folding Funnels

Energetic Pathways to Function

VERY IMPORTANT: Energetic difference between folded and

unfolded proteins ~ equivalent to 1-2 non-covalent interactions

Forces That Hold Proteins Together

Covalent (primary structure)
Single bonds: C-H, C-C, C-N, C-O ~90 kcal/mole

Covalent (secondary and tertiary structure)

Disulfide: S-S, ~60 kcal/mole
Form after protein is folded by non-covalent bonding
Can be intramolecular or between separate chains
Most often found in excreted proteins (for extra stability)

Noncovalent (generally < 5 kcal/mole)

H-bonds (NOTE: Primary for secondary structure)
Hydrophobic
Ionic
van der Waals

Forces That Hold Proteins Together

Covalent (primary structure)
Single bonds: C-H, C-C, C-N, C-O ~90 kcal/mole

Covalent (secondary and tertiary structure)

Disulfide: S-S, ~60 kcal/mole
Form after protein is folded by non-covalent bonding
Can be intramolecular or between separate chains
Most often found in excreted proteins (for extra stability)

Noncovalent (generally < 5 kcal/mole)

H-bonds (NOTE: Primary for secondary structure)
Hydrophobic
PROTEINS ARE STABILIZED
GENERALLY
Ionic
BY <2 NON-COVALENT BONDS
van der Waals

Reflection
Can you imagine why
most living organisms
are sensitive to
elevated
temperature?

What would you

imagine would
happen to protein
structure?