Download The peptide bond is rigid and planar

Level
Description
Bonds
Primary
Sequence of amino acids in
proteins
Covalent (peptide bonds)
Secondary
Structural motifs in proteins: αhelix and β-sheet
Hydrogen bonds (between
NH and CO groups in
backbone)
Tertiary
Folding up of polypeptide chain
Various: covalent, ionic,
H-bonds, van der Waals,
hydrophobic
Quaternary
Association of protein subunits
into larger assemblies
Various
The peptide bond is rigid and planar
Trans
10% Pro has cis conformation
Phe-Pro
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Backbone Dihedral Angles
Three Bonds
N-Cα bond – phi angle (Φ)
Cα-C bond – psi angle (Ψ)
O
C
R
H Cα
N
H
R
C
O H
H
N
CO
Φ = -90o
R
CO H Cα
N
H
H R
N HN
H
Cα
O
C
O
NH
Ψ = -90o
Adapted from “Introduction to Protein Structure” by Branden & Tooze
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Certain values of Φ and Ψ are not permitted due to steric hindrance.
Observed
Glycine
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Ramachandran plot for Ala residues
β strand: Φ = -119o, Ψ = 113o
α helix: Φ = -57o, Ψ = -47o
Ramachandran plot of pyruvate kinase
Glycine can have any dihedral angles
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5
α-helix
310 helix π-helix
Three Regular
Polypeptide Helices
α-helix
310-helix
π-helix
phi
psi
-57.8 -47.0
-74.0 -4.0
-57.1 -69.7
Idealized model of the
conformations of polyalanine
are displayed.
6
CO (i) to NH (i+4)
NH (i) to CO (i-4)
1
2
3
4
5
The α helix is a common protein secondary structure
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Helix Wheel
Hydrophilic
Hydrophobic
Amphipathic
Helix Dipole
L-Amino acid forms right-handed α helix
Counterclockwise
NH3+
COO-
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α-helix is a dipole moment.
Amino acid sequence affects a helix stability
1
2
3
4
5
? Interaction between D100 and R103
9
1
2
3
10
β strands to β sheet
11
5
4
2
3
1
1 3 2 4 5
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Twist of β Sheet
• The classical beta sheets originally proposed
are planar but most sheets observed in globular
proteins are twisted (0 to 30 º/ residue).
• Antiparallel beta sheets are more often twisted
than parallel sheets. This twist is always of the
same handedness, but unfortunately, it has
been described using two conflicting
conventions in the literature. If defined in
terms of the progressive twist of the hydrogenbonding direction, the twist is right-handed.
• Two-stranded beta strands show the largest
twists.
β-Bulge
• Another irregularity found in antiparallel beta
sheets is the hydrogen-bonding of two residues
from one strand with one residue from the other
called a beta bulge.
• Bulges are most often found in antiparallel sheets
with ~5 % of bulges occurring in parallel strands
(Richardson, 1981). Bulges, like "Turns" effect the
directionality of the polypeptide chain.
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Turns
• Turns are the third of the three "classical" secondary structures.
Approximately one-third of all residues in globular proteins are
contained in turns that serve to reverse the direction of the
polypeptide chain.
• This is perhaps not so surprising since the diameter of the
average globular protein domain is roughly 25 Å (an extended
polypeptide conformation would require ~7 residues to traverse
the domain before having to change directions).
• Turns are located primarily on the protein surface and
accordingly contain polar and charged residues. Antibody
recognition, phosphorylation, glycosylation, hydroxylation, and
intron/exon splicing are found frequently at or adjacent to turns.
Turns
β turn: 4 residues; CO (1st residue) to NH (4th residue)
γ turn: 3 residues: ?
Amino acid residues P and G tend to have turn structure.
XPGX
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Type I Turn.
• The hydrogen bond
between CO of residue i
and NH of residue i+3.
• The backbone dihedral
angles are (-60, -30) and
(-90, 0) of residues i+1
and i+2, respectively, for
the type I turn.
• Proline is often found in position i+1 in type I turns as its phi angle
is restricted to -60 and its imide nitrogen does not require a hydrogen
bond. Glycine is favored in this position in the type II' as it requires
a positive (left-handed) phi value.
•P2G3
Type II Turn.
• The hydrogen bond between
CO of residue i and NH of
residue i+3.
• The backbone dihedral angles
are (-60, 120) and (80, 0) of
residues i+1 and i+2,
respectively, for the type II
turn.
• Glycine is favored in this
position in the type II' as it
requires a positive (lefthanded) phi value.
15
Type III Turn.
• The hydrogen bond between CO of residue i and NH of
residue i+3.
• This is a single turn of right-handed (III) and left-handed (III')
310 helix. The backbone dihedral angles are (-60, -30) and (60, -30) of residues i+1 and i+2, respectively, for the
classical type III turn.
Gamma Turn
• The hydrogen bond
between CO of residue
i and NH of residue
i+2.
• The dihedral angles of
residue i+1 are (70, 60) and (-70, 60) for
phi and psi of the
classical and inverse
gamma turns.
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Loop regions are at the surface of protein molecules
Loops
• In Leszczynski & Rose (1986), out of 67
proteins surveyed, they tabulated 26 % helix,
19% sheet, 26 % turns and 21 % in loops.
• These loop structures contain between 6 and 16
residues and are compact and globular in
structure. Like turns, they generally contain
polar residues and hence are predominantly at
the protein surface.
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Common secondary structures have characteristic
bond angles and amino acid content
Preferred Residues for β Sheet and Turns
• Eight most common
residues for beta-sheet
Val, Ile, Tyr, Trp,
Phe, Leu, Cys, Thr
• Eight least common
residues for beta-sheet
Glu, Asp, Pro, Ser,
Lys, Gly, Ala, Asn
• Eight most common
residues for turns
Gly, Asn, Pro, Asp,
Ser, Cys, Tyr, Lys
• Eight least common
residues for turns
Ile, Val, Met, Leu,
Phe, Ala, Glu, Trp
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Globular proteins have common structural patterns
tertiary structure
domain
motif
secondary structure
primary structure
Motif or supersecondary structure: A commonly occuring substructure,
usually comprising two to three secondary structures.
Super Secondary Structures (Motifs)
• Simple combinations of a few secondary structure
elements with a specific geometric arrangement
are called super secondary structures or motifs.
• They may have functional and structural
significance.
• Common motifs:
– Helix-turn-helix
β-hairpin, β-meander
β-barrel, Geek key
βαβ
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Helix-Turn-Helix Motif
• Two α helices that are connected by a short loop region in a
specific geometric arrangement constitute a helix-turn-helix
motif. (a) the DNA-binding motif and (b) the calciumbinding motif, which are present in many proteins whose
function is regulated by calcium.
EF-hand Calcium-binding Motif
• The calcium atom is bound to one of the motifs in the muscle
protein troponin-C through six oxygen atoms: one each from
the side chains of Asp (D) 9, Asn (N) 11, and Asp (D) 13; one
from the main chain of residue 15; and two from the side chain
of Glu (E) 20. In addition, a water molecule (W) is bound to
the calcium atom.
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Amino Acid Sequences of EF-hand Motifs
1
3
5
7
9
12
The side chains of hydrophobic residues on the flanking helices
form a hydrophobic core between the α helices
The β Hairpin Motif
Bovine Trypsin Inhibitor
Snake Venom Erabutoxin
• The hairpin motif is very frequent in β sheets and is built up
from two adjacent β strands that are joined by a loop region.
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Greek Key Motif
• The Greek key motif is found in antiparallel β sheets when
four adjacent β strands are arranged in the pattern shown as a
topology diagram in (a). The three dimensional structure of the
enzyme Staphylococcus Nuclease shown in (b) in blue and red
is also a Greek key motif.
Forming Greek Key Motif
• Suggested folding pathway from
a hairpin-like structure to the
Greek key motif.
• Beta strands 2 and 3 fold over
such that strand 2 is aligned
adjacent and antiparallel to
strand 1.
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β-hairpin motif
?
Greek key motif
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Greek key motif
staphylococcus nuclease
Topology diagram
aspartate
transcarbamoylase
flavodoxin:
redox protein
plastocyanin:
electron carrier
25
β−α−β Motif
• Two adjacent parallel β strands are usually connected by
an α helix from the C-terminus of strand 1 to the Nterminus of strand 2.
• Most protein structures that contain parallel β sheets are
built up from combinations of such β−α−β motifs.
β−α−β motif
right hand
left hand
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β−α−β Handedness
• The β−α−β motif can in principle have two "hands."
• (a) This connection with the helix above the sheet is found
in almost all proteins and is called right-handed because it
has the same hand as a right-handed α helix.
• (b) The left-handed connection with the helix below the
sheet.
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Domains are built from structural motifs
triosephosphate isomerase
protein structure
domain
motif
secondary structure
primary structure
P53
DNA-binding domain
sheet-turn-helix
α-helix & β-sheet & turn
linear chain
28
Structural domains in the polypeptide troponin c
Domains are regions of contiguous polypeptide chain that have been described as
compact, local, and semi-independent units.
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