Download Basics of protein structure Me Introduction to protein structure Four

10/28/10
Me
Basics of protein structure
Basics of protein structure (Chapter 2)
Also check appendix A:
“Bonds and energetics of macromolecules”
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Tel 018-4714177, 070-5988391
Nucleic acid structure (Chapter 3) contains parts
beyond this course
Translation (Chapter 8)
Membrane proteins (Chapter 10)
Four structure levels
Introduction to protein
structure
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Why do we need to know
structure to understand
macromolecules?
Proteins consist of L amino acids
pKa ≈8
pKa ≈3
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Table 2.1
Salt bridges - interactions between charged side chains
Side chains that
can participate in
hydrogen bonds
Primary structure
Direction: N-terminus => C-terminus
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The polypeptide chain
α-carbon
R1 H
H 2N
Cα
C
O
N-terminus
R3 H
O
H
N
C-terminus
carbonyl
group
side chain
Cα
H
peptide
bond
R2
C
The polypeptide conformation
N
H
O
Cα
C
O
amide
nitrogen
OH
H 2N
Cα
H
C
OH
R4
peptide bond formed
by elimination of
H2O
Allowed backbone torsion angles:
exercize
Ramachandran diagram
Ala
Gly
psi
Ramachandran diagram:
sterically allowed torsion
angles
phi
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Side chain conformations
•  Ile and Thr have chiral Cβ.
α-helix (3.613 helix)
Right-handed
3.6 residues per turn
13 atoms in the ring formed by H-bond
•  Preferred torsion angles in side chains (rotamers)
based on staggered conformations.
9 Aspartic acid
rotamers
Properties of the α helix
Helix dipole
•  All side chains point in the same direction
C-terminus
N-terminus
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Other types of right-handed helices
310 helix
H-bonding to N+3
Antiparallel
β-sheet
π helix (4.116)
H-bonding to N+5
Table 2.3!!
Parallel
β-sheet
Mixed β-sheet
Parallel
Anti-parallel
Thioredoxin
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Topology - the way the secondary
structure elements are connected
Other types of
secondary structure
β-strand
β-bulges
Polyproline helices
(collagen)
α-helix
Turns
(several kinds)
Tertiary structure – create a complex surface
topography that can interact with other (small
or large) molecules
Anti-parallel beta sheets
N
Beta
C
hairpin
open
4-stranded
up-and-down
sheet
Closed
cylinder
7-bladed
propeller
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Parallel beta sheets
Greek key
3
2
1
4
Jelly roll
beta helix
5
4
7
2
1
8
3
6
The βαβ unit
The βαβ unit
C
6
5
4
1
2
3
N
Rossmann fold
TIM barrel (Triose phosphate isomerase)
Active site at C-terminal end of beta strands.
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Alpha domains – helices pack with certain
angles
Myohemerythrin Let’s find out which are the preferred
packing angles
25°
45°
Myoglobin Helix packing
20°
N C
Four-helix bundle
50°
Globin fold
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Classification of domains
Alpha domains Beta domains Cross‐linked domains Transducin-α: domains can be inserted
Alpha/beta domains Alpha + beta domains Domain swapping
Mosaic proteins
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Protein folding
•  Proteins are only marginally stable
ΔG=ΔH‐TΔS Protein folding
landscape
1 105
dG
dH
TdS
Energy (cal/mol)
5 104
0
-5 104
-1 105
150
200
250
300
350
400
450
T (K)
Hydration shell
Hydrophobic core
small caviAes allow flexibility 11
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Metal ions in proteins
Further stabilisation
by disulfide bonds,
metal ions and cofactors
DaAT: pyridoxal phosphate myoglobin: heme 12