Download Monomer/ Oligomere Polymer/Aggregat Zucker Glucose

Zucker
Fettsäuren
Nukleinsäuren
Aminosäuren
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Monomer/ Oligomere
Polymer/Aggregat
Glucose,
Polysaccharide
Energie, Zellmarker
Strukturbausteine
Lipide, Fett
Membranen
Energiespeicher
Kompartmentisierung
ATP, cAMP
RNA, DNA
Energie, Signalsubstanzen
Informationsspeicher
Peptide
Proteine,
Hormone
Enzyme. Motoren, molekulare
Erkennung
1
Ribosomale Proteinsynthese
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•mehrere rRNA Stränge
•> 50 Proteine
•Durchmesser ~21nm
2
in vitro:
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Coupling Efficiency Vs. Peptide Length
Peptide
Length
Coupling
Efficiency
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
0.995
0.98
0.96
0.93
0.91
0.89
0.86
0.84
0.82
0.80
0.78
0.76
0.74
0.73
0.71
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Coupling Coupling Coupling
Efficiency Efficiency Efficiency
0.99
0.95
0.91
0.87
0.83
0.79
0.75
0.71
0.67
0.63
0.60
0.58
0.55
0.53
0.50
0.98
0.92
0.83
0.75
0.68
0.62
0.56
0.50
0.45
0.41
0.37
0.34
0.30
0.27
0.25
0.97
0.89
0.76
0.65
0.56
0.48
0.41
0.36
0.30
0.26
0.22
0.19
0.17
0.14
0.12
0.96
0.85
0.69
0.56
0.46
0.38
0.31
0.25
0.20
0.17
0.14
0.11
0.09
0.07
0.06
4
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Different graphical representations of the same protein
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Faltungsproblem
Mother nature has no
folding probem,
but we do!
Konformation eines Proteins
als Random Walk:
Gitter-Modell:
Kleines Protein mit 100 Aminosäuren
=> Mögliche Konformationen: 3100≈
1030
Interne Dynamik typ ns
⇒Zeit, um alle möglichen
Kombinationen durchzuspielen
≈ 1021
s
Vergleiche: Alter des Universums ≈ 1020 s !
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Protein Folding Related Diseases
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10
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11
Proteinfunktionen
•
•
•
•
•
•
•
Zellgerüst
Motoren
Sensoren
Photosynthese
Enzymatische Katalyse
Ionenkanäle
.....
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Beispiel: Die Sehkaskade
Stäbchenzelle
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Proc Natl Acad Sci U S A. 2002 April 30;
99(9): 5982–5987.
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Photozyklus
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Chemical modifications and processing alter the biological
activity of proteins
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M 567/ 568 Lö 27, 28, 31
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Lö 28
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24
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Disulfidbrücken stabilisieren Proteine
(können in seltenen Fällen auch Knoten bilden)
HUMAN AGOUTI RELATED PROTEIN
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Lö 38
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Lö 28
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Table 3-2. Covalent and Noncovalent Chemical Bonds
Strength (kcal/mole)*
Bond Type
Length (nm)
In Vacuum
In Water
Covalent
Ionic
Hydrogen
van der Waals attraction
(per atom)
0.15
0.25
0.30
0.35
90
80
4
0.1
90
3
1
0.1
*. The strength of a bond can be measured by the energy required to break it, here given in kilocalories
per mole (kcal/mole). ( One kilocalorie is the quantity of energy needed to raise the temperature of 1000 g of
water by 1C. An alternative unit in wide use is the kilojoule, kJ, equal to 0.24 kcal.) Individual bonds vary a
great deal in strength, depending on the atoms involved and their precise environment, so that the above
values are only a rough guide. Note that the aqueous environment in a cell will greatly weaken both the ionic
and the hydrogen bonds between nonwater molecules (Panel 3-1, pp. 92-93). The bond length is the centerto-center distance between the two interacting atoms; the length given here for a hydrogen bond is that
between its two nonhydrogen atoms.
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Steric limitations on the bond
angles in a polypeptide chain.
(A) Each amino acid contributes
three bonds (colored red) to its
polypeptide chain. The peptide bond
is planar ( gray shading) and does
not permit rotation. By contrast,
rotation can occur about the C α-C
bond, whose angle of rotation is
called psi (ψ), and about the N-C
α bond, whose angle of rotation is
called phi (). The R group denotes
an amino acid side chain. (B) The
conformation of the main-chain
atoms in a protein is determined by
one pair of phi and psi angles for
each amino acid; because of steric
collisions within each amino acid,
most pairs of phi and psi angles do
not occur. In this so-called
Ramachandran plot, each dot
represents an observed pair of angles
in a protein. (B, from J. Richardson,
Adv. Prot. Chem. 34:174-175,
1981.)
33
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Lovell et al. 2003 Proteins 50:437
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Glyzin, Pre-Prolin, Prolin
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BMC Struct Biol. 2005; 5: 14.
doi: 0.1186/1472-6807-5-14.
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A β−sheet is a common
structure formed by
parts of the polypeptide
chain in globular
proteins. At the top, a
domain of 115 amino
acids from an
immunoglobulin molecule
is shown; it consists of a
sandwich-like structure of
two β− sheets, one of
which is drawn in color.
At the bottom, a perfect
antiparallel β− sheet is
shown in detail, with the
amino acid side chains
denoted R. Note that
every peptide bond is
hydrogen-bonded to a
neighboring peptide bond.
The actual sheet structures
in globular proteins are
usually less regular than
the β− sheet shown here,
and most sheets are
slightly
twisted
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An α-helix is another common structure formed by parts of the polypeptide chain in proteins.
(A) The oxygen-carrying molecule myoglobin (153 amino acids long) is shown, with one region of
α- helix outlined in color. (B) A perfect α- helix is shown in outline. (C) As in the β-sheet, every
peptide bond in an α- helix is hydrogen-bonded to a neighboring peptide bond. Note that for clarity
in (B) both the side chains [which protrude radially along the outside of the helix and are denoted by
R in (C)] and the hydrogen atom are omitted on the α- carbon atom of each amino acid
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Motifs are regular combinations of secondary structures
A coiled coil motif is
formed by two or more helices
wound around one another
e.g. Collagen
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Three levels of organization of a protein. The three-dimensional structure of a protein can be described
in terms of different levels of folding, each of which is constructed from the preceding one in hierarchical
fashion. These levels are illustrated here using the catabolite activator protein (CAP), a bacterial gene
regulatory protein with two domains. When the large domain binds cyclic AMP, it causes a conformational
change in the protein that enables the small domain to bind to a specific DNA sequence. The amino acid
sequence is termed the primary structure and the first folding level the secondary structure. As indicated
under the brackets at the bottom of this figure, the combination of the second and third folding levels
shown here is commonly termed the tertiary structure, and the fourth level (the assembly of subunits) the
quaternary structure of a protein
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The information for protein folding is encoded in the sequence
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Primary and secondary structure in hemagglutinin
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Tertiary and quaternary structure in hemagglutinin
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Up To Date No Unified Folding Theory
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Folding Funnel
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Folding of proteins in vivo is promoted by chaperones
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