7/24/2019 Scale of Cellular World
1/43
Object Real Size X 106
Water 0.28 nm 0.28 mm
Alanine 0.5 nm 0.5 mm
Diam. DNA 2.5 nm 2.5 mmHemoglobin 7.0 nm 7 mm
Ribosome 20 nm 2 cm
Polio Virus 30 nm 3 cmMitochondrion 1500 nm 1.5 m
E. coli 2000 nm 2 m
Liver cell 20,000 nm 20 m
Perspective:
Scale of the Cellular World
7/24/2019 Scale of Cellular World
2/43
7/24/2019 Scale of Cellular World
3/43
pH is a measure of the acidity or basicity of an
aqueous solution
pH ~ -log[H+]
pH>7 is basic
pH
7/24/2019 Scale of Cellular World
4/43
Can you think of an
example in your body
where the pH is not
neutral (i.e., near pH7)??
Reflection
7/24/2019 Scale of Cellular World
5/43
Hydrogen bonds
Shared hydrogen between two molecules or parts
of a molecule
Non-covalent bonding
in biological systems
7/24/2019 Scale of Cellular World
6/43
Ionic/electrostatic interactions
Non-covalent bonding
in biological systems
7/24/2019 Scale of Cellular World
7/43
Hydrophobic interactions/forces
Non-covalent bonding
in biological systems
7/24/2019 Scale of Cellular World
8/43
Fig. Geckos climb on sheer
surfaces using van der Waals
forces between the surface
and microscopic projectionson their footpads
van der Waals Interactions
Non-covalent bonding
in biological systems
7/24/2019 Scale of Cellular World
9/43
IMPORTANT:
Approximate Bond Strengths
7/24/2019 Scale of Cellular World
10/43
Promotes assembly
Occurs spontaneously
Driven by interaction energy
Large number of small forces creates flexibility of
structures
Example: Membranes/lipid bilayer
Non-covalent Bonding Essential to Life
7/24/2019 Scale of Cellular World
11/43
Why are the
properties of
water soessential to life
as we know it?
Reflection
7/24/2019 Scale of Cellular World
12/43
Order of amino acids determined bynucleotide 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 semesterBottom line: DNA sequence linked to RNA
sequence linked to protein sequence
Proteins Composed of Amino Acids
7/24/2019 Scale of Cellular World
13/43
Amino Acid Structure
7/24/2019 Scale of Cellular World
14/43
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
7/24/2019 Scale of Cellular World
15/43
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
Properties of Side Chains Important
http://www.wiley.com/college/boyer/0470003790/animations/acideroids/acideroids.htmhttp://www.wiley.com/college/boyer/0470003790/animations/acideroids/acideroids.htm7/24/2019 Scale of Cellular World
16/43
Amino
Acid
Structures
7/24/2019 Scale of Cellular World
17/43
Only imino acid:
Proline
7/24/2019 Scale of Cellular World
18/43
Amino
Acid
Structures
Annotated
7/24/2019 Scale of Cellular World
19/43
Why are the
properties of the
amino acid sidechains
important?
Reflection
7/24/2019 Scale of Cellular World
20/43
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
7/24/2019 Scale of Cellular World
21/43
Proteins are written from N-terminus to C-
terminus 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
PROTEIN STRUCTURE
7/24/2019 Scale of Cellular World
22/43
In the 1930s William Astbury studiedwool and hair using X-ray fiber diffraction
(similar to DNA studies)
Data showed coiled molecular structure
that he called alpha (later to become a-
helix)
When heated or stretched, another pattern
was observed that he called beta (later to
become b-structure or b-sheet)
Patterns of Protein Structure
7/24/2019 Scale of Cellular World
23/43
Link to YouTube video about alpha helix
Identified by PaulingHistoric Article
Alpha Helical Structure
http://www.youtube.com/watch?NR=1&v=eUS6CEn4GSAhttp://www.youtube.com/watch?NR=1&v=eUS6CEn4GSA7/24/2019 Scale of Cellular World
24/43
Link to YouTube video about alpha helix
Backbone hydrogenbonding between
amino and carbonyl
separated by 4residues
Alpha Helical Structure
http://www.youtube.com/watch?NR=1&v=eUS6CEn4GSAhttp://www.youtube.com/watch?NR=1&v=eUS6CEn4GSA7/24/2019 Scale of Cellular World
25/43
Link to YouTube video about alpha helix
Backbone hydrogenbonding within the
same strand
Alpha Helical Structure
http://www.youtube.com/watch?NR=1&v=eUS6CEn4GSAhttp://www.youtube.com/watch?NR=1&v=eUS6CEn4GSA7/24/2019 Scale of Cellular World
26/43
Link to YouTube video about alpha helix
Can have interactionsof R groups (not shown
here in poly-Ala) to
stabilize helix
Alpha Helical Structure
http://www.youtube.com/watch?NR=1&v=eUS6CEn4GSAhttp://www.youtube.com/watch?NR=1&v=eUS6CEn4GSA7/24/2019 Scale of Cellular World
27/43
Link to YouTube video about beta sheets
Backbone hydrogen bonding
between strands
Beta-Sheet Structure
http://www.youtube.com/watch?v=wM2LWCTWlrEhttp://www.youtube.com/watch?v=wM2LWCTWlrE7/24/2019 Scale of Cellular World
28/43
Backbone hydrogen bondingbetween strands
Note interaction between R
groups (does this limit R size?)
Beta-Sheet Structure
7/24/2019 Scale of Cellular World
29/43
Orientation can be
anti-parallel
orparallel
b-Sheet Structure
7/24/2019 Scale of Cellular World
30/43
7/24/2019 Scale of Cellular World
31/43
Beta-
SheetStructure
7/24/2019 Scale of Cellular World
32/43
Why do you think thatthe a-helix and b-sheet
are each referenced as
secondary structure?
How does the energy of
these structures compareto the energy of the
peptide bond?
Reflection
7/24/2019 Scale of Cellular World
33/43
What contribution doesthe side chain of each
amino acid make to
secondary structure?
Would you expect all
amino acids participatein secondary structure?
Reflection
7/24/2019 Scale of Cellular World
34/43
Primary Structure: Amino acid sequence
Secondary Structure:
a-helix/b-sheet
Tertiary Structure:
Folding into 3-dimensions
Quaternary Structure:
Assembly into higher oligomers
Levels of Protein Structure
7/24/2019 Scale of Cellular World
35/43
d l d ld
7/24/2019 Scale of Cellular World
36/43
Stabilizing energy for protein folding:
Primarily non-covalent interactions
Disulfide
bond
formation
(covalent
bond) can
stabilize
protein fold
Bonds Utilized in Protein Folding
7/24/2019 Scale of Cellular World
37/43
Link to another YouTube video about protein folding
Link to YouTube video about protein folding
Interactions occur rapidly and result in the folded structure
Process is dynamic AND Structure is dynamic
Bringing Alpha Helices/Beta Sheets
Together in a Folded Structure
http://www.youtube.com/watch?v=_xF96sNWnK4&NR=1http://www.youtube.com/watch?feature=fvwp&NR=1&v=fvBO3TqJ6FEhttp://www.youtube.com/watch?feature=fvwp&NR=1&v=fvBO3TqJ6FEhttp://www.youtube.com/watch?v=_xF96sNWnK4&NR=17/24/2019 Scale of Cellular World
38/43
Protein Folding Funnels
Energetic Pathways to Function
7/24/2019 Scale of Cellular World
39/43
Large energy penalty for loss of entropy think of it as loss of options for
different states so that the overall difference in energy betweenfolded/unfolded is small!
Protein Folding Funnels
Energetic Pathways to Function
7/24/2019 Scale of Cellular World
40/43
VERY IMPORTANT: Energetic difference between folded and
unfolded proteins ~ equivalent to 1-2 non-covalent interactions
Protein Folding Funnels
Energetic Pathways to Function
7/24/2019 Scale of Cellular World
41/43
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 afterprotein 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
h ld h
7/24/2019 Scale of Cellular World
42/43
PROTEINS ARE STABILIZED
GENERALLY
BY
7/24/2019 Scale of Cellular World
43/43
Can you imagine whymost living organismsare sensitive toelevated
temperature?
What would you
imagine wouldhappen to proteinstructure?
Reflection