Lesson 7: Levels of Protein Organization at Ceu Universidad San Pablo

Levels of Protein Organization

LESSON 7. LEVELS OF PROTEIN ORGANIZATION
O
PEPTIDE BOND
PRIMARY STRUCTURE
· SECONDARY STRUCTURE
SUPERSECONDARY STRUCTURES
· TERTIARY STRUCTURE
· QUATERNARY STRUCTURELESSON 7. LEVELS OF PROTEIN ORGANIZATION
O
PEPTIDE BOND
· PRIMARY STRUCTURE
SECONDARY STRUCTURE
· SUPERSECONDARY STRUCTURES
· TERTIARY STRUCTURE
· QUATERNARY STRUCTURECEU
Universidad
San Pablo

Peptide Bond Formation

PEPTIDE BOND
Peptide bond
R
1
0
+HIN -Ca- C
H
I
I
0
0
+
THEN -Ca-C
0
Peptide bond
R
R
1
2
I
0
11
-
TH_N-C& C-N-Ca-C
I
-
H
H
0
H
The creation of the peptide bond.
When bonding something
automatically changes, the 2 groups
involved in the peptide bond when
binding together they lose the ability
to ionise, to gain or lose an electron.
The only groups responsible of the
charge it's the side chain of the
amino acid, the carbon, and the
amino group.
Peptide bond, form a very important
bond to stabilise hydrogen bond, and
create in each peptide bond 2
hydrogen bonds. One as a donner
and one as an acceptor, they can
bind to another 2 hydrogen bonds, to
reinforce the structure. To keep
structure of the protein.

+
H20
2
1
N-terminus
C-terminus
I
H
2
RCEU
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Peptide Bond Stability and Structure

Resonance and Stability of Peptide Bonds

PEPTIDE BOND
Peptide bond
2. The real structure it's a coexistence of the 2
resonance structures. Really hard to break. If we want
to break the peptide bind we need enzymes.
- High stability
- Elements in the bond cannot be charged, but may form hydrogen bonds.
- Resonance hybrid:
Bond length: 1,32 A
Intermediary between:
Single bond C-N = 1,49 A
Double bond C-N = 1,27 Ă
1
2
Co
C
N
-C=N-111
(60%)
1.When analyse the
peptide bond, like the
length, the distance
between the carbon
and nitrogen pf the
peptide bond, it's
something in between
a single and a double
bond. Stronger than a
single and weaker than
a doubled. The reason
it's because it exists as
a resonance.

Planar Peptide Bond and Isomers

- Planar peptide bond: cis-trans isomers
O
H
R
C
C
C
N
H.
R
H
Better, more
storage
effect.
Trans isomer
(lower steric impediment)
More stable
H
3. The consequence of
being so strong. Since the
bond is something in
between it can't rotate, the
elements of the peptide
bond can't rotate. All
H
C
R
H
located in the same
C
C
O
plane. The alpha carbons
are connecting the bond,
they act as a bisagra. We
need to fit all the elements
N
in order for them to not
H
collide. So they can be
more stable.
Other possibility it's to have
Cis isomer
them all looking at the same
(higher steric impedimentde, less stable
Less stableCEU
Universidad
San Pablo

Peptide Bond Nomenclature

PEPTIDE BOND
NOMENCLATURE
Peptide backbone
α
R1
α
+H3N -CH-CO-NH-CH-CO-NH-CH-CO-
1
R2
Sequence direction
N-terminal
residue
(synthesis direction)
C-terminal
residue
To name a protein, we are going to follow the same direction, to name the amino acid, we
need to name them all in the same direction, and finish in -yo except the last one, that
conserves the name, or use the abbreviation, so we have to separate the amino acids by a -.
OH
CH2
Ħ
N
H3N
0
(serine)
(leucine)
Serylleucine or Ser-Leu
H
CH3
e
N
e
H3N
H3N
0
CH2
OH
Leucylserine or Leu-Ser
OH
Leu-Tyr-Ala
I-Z
N
H
..
α
R3
Rn
α
·NH-CH-COO"
-CEU
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Peptide Bond Rotation and Conformational Angles

PEPTIDE BOND
Unfavourable rotation
(hybrid bond)
O
H
R
O
H
R
O
H
R
O
H
H
Φ
H
C
C
N
N
.C
C
N
C
C
N
N
C
α
α
α
α
α
α
α
C
N
C
C
N
C
C
N
C
C
N
/
H
O
R
H
O
R
H
O
R
H
H
R®
H
/
Ψ
H
H
/
Free rotation around single bonds
Conformational angles
Y (psi): C-Cx rotation angle
+ (phi): N-Cx rotation angle
All elements attached to alpha carbon, those bonds can rotate. Angles are really important, the combination
between thee two are going to give us the form and structureGet all the elements as far form each other.CEU
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Ramachandran Plot and Conformations

PEPTIDE BOND
Very limited combination angles, most of them will make the bonds crash to each other, etc.
Conformational angles
We can rotate the phi and psi angle.
W have to get the methyl group
further form the peptide bond, so
there's no interaction.
Amide plane
H
0
Amide plane
Co
N
C
C
N
0
Side group - R
H
H
parallel ß
sheet, planar
Antiparallel ß
sheet, planar
Collagen a helix
180°
90°
90°
o
a helix
(left)
0o
Ψ
-90°
a-hélice
(right)
-180º
-180°
-90º
0º
90°
180°
Φ
-
90°
RAMACHANDRAN PLOT
(plausible conformations)
General
Gly
W =- 60 °
@=+180 º
Only combinations possible are in purple.
For gly, we have more chances since the side chain it's not a issue, and the size
it's very small.CEU
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Structural Levels of Proteins Overview

STRUCTURAL LEVELS OF PROTEINS
aa1- aa2- aa3-
- aan PRIMARY STRUCTURE
0
SECONDARY STRUCTURE
2
1
1
SUPERSECONDARY STRUCTURE
TERTIARY STRUCTURE
-
QUATERNARY STRUCTURE
STRUCTURAL DOMAINSLESSON 7. LEVELS OF PROTEIN ORGANIZATION
PEPTIDE BOND
PRIMARY STRUCTURE
O SECONDARY STRUCTURE
· SUPERSECONDARY STRUCTURES
· TERTIARY STRUCTURE
· QUATERNARY STRUCTURECEU
Universidad
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Primary Structure of Proteins

PRIMARY STRUCTURE
Gin
H3N+- Gly
Ile
Val
Cys
Ala
-4-4-
Ser
Val
Leu
Pro
Cys
Asp
Arg
Lys
-COO-
Asn
Phe
Tyr
Lys
Thr " Leu
His
Terminal ends are
ionized
physiologie
PH=7
charge
at PH= 7
COO -
NH3
PH=1- 30
PH= 7 - 10
PH= 13 > 20
we
have to
look at the
ends
pka : 2
COOH > COO-
9
pka :
NH3+ > NH2
195
always pluto!
nized at
H 3 N Physiologie
PH=7
us - Glu - Ala - Ile - , COO always proto
+
nized at
neutral
neutral
NH3
The primary structure, tells us the
sequence of the nucleotides form N
end to the C end. The information
that we can get, about the potential
sílfide bridges, we can also know
the charge of the amino acid,
residues that are charged, at a
physiological pH
GluLESSON 7. LEVELS OF PROTEIN ORGANIZATION
· PEPTIDE BOND
· PRIMARY STRUCTURE
SECONDARY STRUCTURE
· SUPERSECONDARY STRUCTURES
· TERTIARY STRUCTURE
· QUATERNARY STRUCTURE

Secondary Structures of Proteins

Definition and Forms of Secondary Structure

Secondary structures
Fold the proteins, local part of the protein. Are regular
tridimensional folding in portions of the protein.
- Definition
- Main forms of secondary structure
a-helix structure
- Characteristics
- Incorporation to globular structures
- Incorporation to fibrilar structures
ß-sheet structure
- Characteristics
- Incorporation to globular structures
- Incorporation to fibrilar structures
Right-handed N.
m
helix
Left-handed collagen helix
Non-periodic structuresCEU
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Alpha-Helix Structure Details

General Structure and Parameters of Alpha-Helix

SECONDARY STRUCTURES
3 Alpha helix it's going to be maintain by the hydrogen bonds between the peptide planes. We can
get 2 hydrogen bonds per amino acid, one up top, and the amino acid below.
C
a- helix general structure
Cơ
Ca
Co
Parameters
Ca
diameter: 5 Å
(peptide backbone)
Ca
pitch: 5,4 A
3,6 residues per turn
R14
diameter: 5Å
100°
(peptide backbone)
R5
R7
R12
R1
Cơ
C
a
.....
Ca
Ca
Conformational angles:
₡ =- 57º
=- 47º
N
2 The side chains of the amino acid are hanging form the
alpha carbon, are going to be located on the outside of the
helix. Since a complete helix, there are a rotation of 100° to
find the second residue form the fist one.
Top view
R6
R13
R17
R2
R10
Rg
R3
R16
Distance between aa: 1,5 A
rotation: 100°
R1
R11
Ra
RA
R15
Phi and PCI angles, when they get to -57 and -47 we
are going to be able to repeat those angles, and the
protein gets the right handed helix, where peptide
planes are located parallel on our axes. Alpha helix,
and all the peptides planes are parallel to each other
and facing the x axis. We have to remember that in a
turn of helix we can create 4 amino acids. Every
peptide plane has 1 amino acid on top and 1 amino
acid at the bottom, separated by 4, or 3,6 amino acids.CEU
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Stabilization of Alpha-Helix by Hydrogen Bonds

SECONDARY STRUCTURES
SCHEMATIC VISION OF THE ATOM
DISPOSITION IN a-HELIX
2. The hydrogen bonds, are located within, which is what we call intracatenary hydrogen bonds, they
are all inside the same chain, up and below.
3 Depending how the radical change, the alpha helix can get destabilised, the parameters can change,
we can stretch out of they can be tighter.
C
C
C
O
N
C
O
H
N
O
H
Ca
N
C
H
O
N
O
Ca
N
H
C
C
H
O
O
N
C
C
H
O
H
O
H
O
H
N
O
C
Ca
H
N
C
Ca
H
O
N
--------
C
Ca
O
H
www-C-N-C-www
H
Ca
1) bonds
N
Stabilization by
INTRACATENARY HYDROGEN BONDS
O
C
backbone
y side
chains on
the outside
N.
C
H
O
Ca
........
...
.........
...
N
N
O
H
www-C -- N -- C-www
H
R
Hydrogen
bonds
I
H
NO
‘R
all phi and psi angles have to be all
the same in order to have this.
O
N
C
O
H
ZI
H
C
Ca
N
C
H
O
N
C
N
H
H
O
Ca
N
C
-....
Ca
N
O
C
O
C
C
I
Ca
HO
N
C
Ca
O
H
N
C
Ca
H
Ca
N
O
N
C
O
Ca
N
H
C
C
O
H
O
H
N
C
O
C
O
HCEU
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Factors Destabilizing Alpha-Helix

SECONDARY STRUCTURES
SIf they are close to the outside of the helix, because of the repulsion or attraction forces between the
peptide bonds.
CH3 CH2 -CH
The Aminoacids that destabilize the w helixbond, because there's a competition, to
form hydrogen bonds, there's a group that has to donate and the other accepts. They are going to break
the hydro
bonds of the structure to form their own hydrogen bonds.
Bulky, ramificated amino acids: ile
sterkt effect)
- Amino acids that form hydrogen bonds:
competition with the hydrogen bonds that stabilize the helix.
Mainly Ser y Thr.
Bulky group too
close to the main
backbone
* - Charged amino acids: Trend to destabilze the helix when
facing each other
- Aromatic amino acids. May stabilize or destabilize the helix
depending on its relative orientation.
Charge amino acids, because it can create repulsion (stretches out the
helix) or attraction of the charges (compresses the helix).
a-helix distorsion
by electrostatic interactions
a-helix
We fold the protein so the hydrophobic side
chains doesn't interact i with the water, so the
other parts of the protein are in charge of
folding and protecting the hydrophobic side
chains.
repulsion
+
atraction
-
.......
-
N
N
Disposition of the aromatic rings
Repulsion trend
M
N
2 amino acimina acids that do not form a belixwhich are
proline and glycine. Proline, has the radical that is cycle, the
angle between carbon and nitrogen can't rotate because it's
Proline
attached to the carbon, and can't get the angular ion we need
for the alpha helix, and woll change the rotation, So they are
usually at the beginning or the end, to change tesudtattlenoand
we can't stabilised the hydrogen bonds, becauseshertesn't
have a hydrogen. CH
Fixed angle
Glycine, the side chains are small hydrogens, but glycine is
perfect amino acid that gives a conformation, so instead of
alpha helix, we ind it has a beta conformation, it' good folding
the proteins.