CLASS: Fundamentals I
DATE: August 11, 2011
PROFESSOR: DeLucas
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SCRIBE: Carolyn Cochran
PROOF: Joe Vaughn
Page 1
Secondary Protein Structure
Secondary Protein Structure
What to know
a. This slide highlights the topics to pay attention to.
b. Pay attention to these things, he does not test on numbers.
Protein secondary structure
a. Hydrogen-bonding (H-bonding), ionic, and Vander wall interactions
are all weak. They are short branch interactions, all things must be
close because are weak interaction.
b. It is the sum of Vander wall interactions that give the strength to
proteins.
c. If talking about longer range interactions aren’t talking about globular
proteins anymore.
i. We would be talking about fibrous proteins like collagen and
keratin.
d. If phi(ϕ) and psi(ψ) bond angles are all equal, will have all same
amino acids, or groups of amino acids.
i. Would have regularity or periodicity in secondary structure.
ii. The way it twists to make a motif would always be the same.
iii. We have peptides that are like this but normally we have a
mixture of all amino acids.
iv. Depending on what amino acids make up a segment, will
determine if it has a different twist or not in the tertiary
structure.
Main Classes of Secondary Structure
a. In all these local secondary structures, hydrogen bonds play a key
role.
i. Can be alpha(α) helix, beta(β) sheet, or turn.
ii. beta turn happens between two beta strands.
What Are the Elements of Secondary Structure in Proteins, and How Are
They Formed?
a. Phi and psi angles are how secondary structures are formed.
b. If you sit on the alpha carbon of an amino acid and look toward
nitrogen or carbonyl oxygen, these angles of rotation are phi and psi.
i. As look toward each from alpha carbon, count the degrees
clockwise to get angle.
Consequences of Amide Plane
a. There are two degrees of freedom per residue for the peptide chain.
b. Responsible for how protein twists to form a tertiary structure
(phi/psi angles).
c. If look at amino acids – some are really good at forming a stable alpha
helixes while others are not.
i. Helps so can look at primary sequence and tell a lot about a
protein.
Diagram – Shows possible conformations about an α-carbon.
CLASS: Fundamentals I
DATE: August 11, 2011
PROFESSOR: DeLucas
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SCRIBE: Carolyn Cochran
PROOF: Joe Vaughn
Page 2
Secondary Protein Structure
a. There are ways you can’t combine the two peptide planes.
i. Purple circles are R groups – these drive how things combine
b. If amino acid is in cis conformation, it brings R-groups so close
together that they are bumping into each other.
i. Can’t have a turn b/t the 2 peptide planes that is that sharp.
c. Usually driven by R-groups interacting with other R-groups or with
other parts of the chain itself.
Protein structure
a. G.N. Ramachandran predicted that because there are certain amino
acids that favor alpha helixes and others that don’t, we should be able
to take proteins we know about and map them and see a 2D grid
where alpha helicases seem to form in terms of phi and psi angles. Do
same thing for beta sheets, keratin, and collagen.
Steric Constraints of ϕ and ψ
a. Diagram is a grid of these psi and phi angles plotted out.
b. You will almost always see hydrophobic amino acids on the inside of a
protein and polar (hydrophilic) ones on the outside.
i. Will still see a few hydrophobic ones on the outside where you
don’t expect it.
c. Will see that alpha helixes that are right-handed.
i. Will also see alpha helixes that are left-handed (as shown in
the diagram top left corner).
1. Seen in many proteins.
2. We do not see them as much though because they are
less stable.
ii. Right-handed more stable because the nitrogen and carboxyl
oxygen are almost linear and line up on the long axis of the
helix.
iii. Left-handed helix is not as linear – thus not as stable.
1. Are not very long, but are still in various regions of
protein
d. Chart shows where most alpha helixes will occur.
i. Dots in purple represent actual angles measured for 1000
residues in 8 proteins.
e. Showing this to show that there are regions that will favor one type of
helix over another and in terms of how phi psi angles will occur. This
causes different secondary structure.
Hydrogen Bonds in Proteins
a. H-bonds between backbone of protein give it stability.
b. Can take one helix of a protein and let it associate with another.
c. These bonds aren’t enough to keep it together but the cumulative
effect is what holds one helix to another.
d. Internally in protein have some of this but hydrophobic r-groups
really cause it to fold.
CLASS: Fundamentals I
DATE: August 11, 2011
PROFESSOR: DeLucas
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SCRIBE: Carolyn Cochran
PROOF: Joe Vaughn
Page 3
Secondary Protein Structure
e. Entropy is driving force that causes protein to fold by eliminating
water and making it randomly associate outside.
i. Hydrophobic r groups don’t want water around so tend to try
to shield themselves from it by interacting with each other.
Protein structure
a. Helical structures also twist within the protein.
i. Allows everything to line up.
b. Beta pleated sheet has a slight right handed twist
i. Has to do with what is more stable as it forms H-bonds
between one strand and another.
c. There is some nomenclature that you should be familiar with:
i. The “n” is the number of peptide units in a helical turn.
1. It is 3.6 residues, which is weird. Scientists thought it
would be a whole number so could have repeating
helixes. What drives the line up is H-bonding though.
ii. The “pitch” is the distance up the axis.
1. For alpha helixes it is 5.4 angstroms. Don’t need to
know number.
d. helixes have chirality. Amino acids are left-handed and are in a right
handed helix and have a net dipole moment through this helix.
Protein structure (cont.d)
a. In biology, everything is transient. Interactions like H-bonds are in
equilibrium. Are not a like a covalent bond that makes up the
backbone of an amino acid.
b. Alpha helix is a stable helix and the designation has 3.6 resins preterm
will see 13 atoms in a term. Tells you that it is an alpha helix.
The α-Helix (diagrams)
a. Shows the linear arrangement of the H-bonding between the NH
group and the carboxyl oxygen.
b. Shows how the planes twist around as you go up the helix. See six
atoms in each peptide plane.
c. Shows steric crowding in the space filling model. Is hard to tell if it is
right handed or left handed.
i. Is why we use the ribbon drawing.
Diagram
a. If count atoms, there are 13 atoms connected covalently in one
complete revolution
Protein structure
a. Alpha helix can be twisted further apart. Allows for less room inside
and is more steric crowding. There is no room for water now at all.
b. Have a 310 helix.
i. Means there is only 10 atoms now instead of 13 in a complete
revolution.
ii. As a result, more steric crowding.
CLASS: Fundamentals I
DATE: August 11, 2011
PROFESSOR: DeLucas
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SCRIBE: Carolyn Cochran
PROOF: Joe Vaughn
Page 4
Secondary Protein Structure
c. Can unwind alpha helix so is more open in the middle and how have
316 helix. 16 atoms in a helix. With this that means the pitch gets
shorter.
d. Pitch gets shorter as helix gets fatter and more atoms added.
Diagram
a. Shows 310
b. Alpha helix – H-bonding is straighter and more stable as a result.
c. π helix.
Exposed N-H and C=O groups at the end of an α-helix can be “capped”.
a. At end of alpha helix what stabilizes it?
b. Average length of alpha helix is around 11 residues.
c. At end of alpha helix though, will have a loop to another alpha helix
or beta sheet.
d. Where the loop comes around, there is now another alpha helix or
part of loop interacting with it. Usually NH group interacts.
e. These are now capped with H-bonds.
Diagram
Table 2.1 Amino Acid Sequences of three α helicases
a. From primary sequence can infer things about proteins.
b. Listed are three example sequences.
i. Green blocks = hydrophobic residue
ii. Blue “”= polar residue
iii. Red “”=charged residue
c. first example, where is helix?
i. Mostly hydrophobic so would think that the helix is buried
deep in protein.
d. Second example, not sure but maybe part of alpha helix is interacting
with another alpha helix, and charged amino acids are facing water.
i. Alpha helix may be on outside of protein with charged amino
acids on outside and phobic regions on inside.
e. Third example – water is all around it. May be where substrate comes
in and binds.
3 diagrams
a. how many residues make a complete turn of an alpha helix?
i. 3.6
ii. divide by 360 degrees. So every 100 degrees get one residue.
iii. Make a wheel and plot residues every 100 degrees and see this
in the chart.
b. In the diagram: Blue atoms = polar; yellow = nonpolar.
c. 3 examples: first one sits on outside of protein; second example is
nonpolar and is inside protein; third is very polar and is surrounded
by water.
d. If see all hydrophobic on one side and hydrophilic on another can see
how sits on the protein.
CLASS: Fundamentals I
DATE: August 11, 2011
PROFESSOR: DeLucas
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SCRIBE: Carolyn Cochran
PROOF: Joe Vaughn
Page 5
Secondary Protein Structure
e. Good way to get an idea where helixes are really exposed on a protein
and which are not.
Space suite picture
Liftoff picture
The β-pleated sheet
a. Sheet itself is formed by beta strands that sit side by side and interact
by H-bonding.
b. Strands can be parallel or antiparallel.
i. If one strand goes N  C and the neighboring one goes CN
the strands run antiparallel.
ii. If strand goes in one direction then loops around and both
strand going same direction is parallel.
1. This is less stable.
c. The antiparallel is most stable because the NH COO are looking
directly at each other and is short h-bond length.
d. Parallel H-bonds are at an angle and bond length isn’t as short, making
them weaker H-bonds.
e. Distance (pitch) between the residues.*
i. Antiparallel – 3.5 angstroms.
ii. Parallel is 3.3 angstroms– because of bonding pattern, tends to
be shorter and this imparts more instability.
1. See this is in proteins all the time.
f. Parallel not as stable –have more strands to make a sheet to help with
stability.
i. Usually 5 or more strands to help build a scaffold.
ii. Often strand twists. And will from a pocket for substrate to
bind somewhere in the protein.
iii. See on interior more.
Diagram – An antiparallel β-pleated sheet
a. See hydrogen bonds going straight across because H-bonds are
straight.
b. Where turns around, loop is short.
i. Called a beta turn.
ii. Not more than 3 amino acids in a loop.
iii. Small amino acids like glycine make up the turn.
Diagram – arrangement of H-bonds in (a)parallel and (b)antiparallel βpleated sheets
a. Can see the difference in angles of H-bonds of parallel versus
nonparallel.
b. Shorter to go 10 residues down the antiparallel strand.
c. To make things as stable as could have to extend peptide out as more.
d. Answer to answer: Enzyme pockets can be in parallel and antiparallel
strands. Beta strands can give structure and strength to a protein.
Diagram
CLASS: Fundamentals I
DATE: August 11, 2011
PROFESSOR: DeLucas
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SCRIBE: Carolyn Cochran
PROOF: Joe Vaughn
Page 6
Secondary Protein Structure
a. Another example of the different bond angles in slide 25.
Protein Structure
a. Beta strands exhibit a right handed twist
b. Very common in proteins.
i. See antiparallel at little more but still see parallel.
Protein structure
a. Can have proteins with both in there. See them mixed together.
1. Example: see slide 26. For parallel sheets have small
hairpin turn then have big loop to go to parallel
configuration.
The beta turn (antiparallel)
a. Usually have small amino acids in the turn.
b. Usually see an R group and NH group interaction after the turn to hold
the sharp turn. This allows alignment of the beta strand with other
beta strand.
Diagram – The structures of two kinds of β-turns.
a. Want the C=O to be point in so can H-bond with the NH group.
Protein structure
a. There are two beta structures for turns
i. Hairpin turn – links 2 antiparallel strands
ii. Crossover connection – links 2 antiparallel sheets.
Diagram – shows types of hairpin loops
a. Type 1 or type 2.
i. Depends on if comes out of paper or into paper.
Fibrous Proteins
a. Have talked about the 3 types of helixes
i. Alpha helix, π helix, and 310 helix.
ii. Talked about beta sheets and strands.
b. Fibrous proteins are involved in strength and structure.
i. Very strong
ii. Insoluble because of types of amino acids in them.
Diagram - (a) coiled coil and (b) Periodicity of Hydrophobic Residues
a. Because amino acids aren’t soluble. Keratin has a heptad repeat meaning that the 1st and 4th amino acid is always hydrophobic. Label
them with letters a,b,c,d,e,f,g. A and D are hydrophobic.
b. If you wrap it around, the first and fourth residue (A and D) pack
against the second one and shield the other hydrophobic regions. So
to make the turns repeat 7 residues perfectly, have 3.5 residues
instead of 3.6. Having 3.6 would cause it to be off a little bit (7.2).
Alpha Keratin
a. Two types : alpha and beta keratin
b. Alpha found in hair, nails, bird beaks.
c. Helical but the ends can be non-helical. Sort of a random structure
with H-bonding but not really random.
CLASS: Fundamentals I
DATE: August 11, 2011
PROFESSOR: DeLucas
Slide 36.
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SCRIBE: Carolyn Cochran
PROOF: Joe Vaughn
Page 7
Secondary Protein Structure
Diagram – Part (a) and (b)
a. What stabilizes it as it wraps around itself is H-bonding and disulfide
bonding.
b. Hair made of keratin.
i. Example: perm
1. Disulfide bonds are being reduced by chemicals so
when disulfide bonds reform they are in different place
and hair is now straight.
2. Putting hair in curlers – break the H-bonds along the
helix of the molecule. Not the disulfide bonds.
Beta Keratin
a. Found in silk, spider webs.
b. Have an alternating sequence - Gly-Ala/Ser-Gly-Ala/Ser
c. Is a beta strand not an alpha helix. Glycine is always sticking up and
bigger R-group is sticking down.
i. So between strands, pack in a way so the glycine’s of both
strands point towards each other.
ii. Alanine and serine pack together because they are the other
amino acids in beta keratin.
Diagram of Silk fibroin
a. Shows how beta keratin packs.
Diagram of spider web fibers.
a. When a spider weaves its web. Alpha keratin is coming out of
stomach and bonds break as it comes out and it reforms beta keratin
mixed with alpha keratin. Some amino acids have neither.
i. This matrix allows spider webs to bend, be tensile, have
strength and be flexible.