2. Human Proteins
• proteins contain C,
H, O, and N
• Made up of 20
amino acids
• amino acids written
in blue are essential
amino acids, meaning
they can not be made
and must be
consumed
3. Proteins
• Proteins serve many functions:
– 1.Structure: collagen and keratin are the chief
constituents of skin, bone, hair, and nails.
– 2. Catalysts: virtually all reactions in living systems
are catalyzed by proteins called enzymes.
– 3. Movement: muscles are made up of proteins
called myosin and actin.
– 4. Transport: hemoglobin transports oxygen from
Transport
the lungs to cells; other proteins transport
molecules across cell membranes.
– 5. Hormones: many hormones are proteins, among
them insulin, oxytocin, and human growth
hormone.
4. Proteins
– 6. Protection: blood clotting involves the protein
fibrinogen; the body used proteins called
antibodies to fight disease.
– 7. Storage: casein in milk and ovalbumin in eggs
store nutrients for newborn infants and birds;
ferritin, a protein in the liver, stores iron.
– 8. Regulation: certain proteins not only control the
expression of genes, but also control when gene
expression takes place.
5. Amino Acids
•Have an alpha- carbon
attached to:
• an amino group
• carboxyl group
• a hydrogen
• an R group
6. Each R group
determines the
properties of the
amino acid
R groups can be
polar, nonpolar,
acidic, basic
7. Each R group
determines the
properties of an
amino acid
R groups can be
polar, nonpolar,
acidic, basic
8. Chirality of Amino Acids
• With the exception of glycine, all proteinderived amino acids have at least one
stereocenter (the α-carbon) and are chiral.
– The vast majority of protein-derived amino acids
have the L-configuration
9. Zwitterions
• amino acids can act as acids and bases
•
•
Amino acids exist in solution as dipolar ions (Zwitterions)
Like buffers, AA’s can act as proton donors or acceptors
– “Amphoteric” compounds or “amphoteric electrolytes”
• Isoelectric point – pH at which all the molecules have equal
positive and negative charges
12. Peptides: how aa are linked
• proteins are long chains of amino acids joined by
amide bonds.
peptide bond:
– amino acids become linked together to form
peptide bonds with the elimination of water
– The reaction takes place between the -COOH of
one amino acid and the -NH2
13. formation of peptide bonds
Peptides and proteins are
polymers of amino acids
• Two amino acids are
covalently joined in
condensation reaction
N-terminal
C-terminal
14. Peptides
– Peptide: A short polymer of amino acids joined by
Peptide
peptide bonds; they are classified by the number of
amino acids in the chain.
– Dipeptide: containing two amino acids joined by a
Dipeptide
peptide bond.
– Tripeptide: containing three amino acids joined by
Tripeptide
peptide bonds.
– Polypeptide: chain containing up to 50 amino acids
Polypeptide
– Protein: A biological macromolecule containing at
Protein
least 30 to 50 amino acids joined by peptide
bonds.
15. 4 levels of protein structure
• Primary – sequence of amino acids
• Secondary – interactions between adjacent amino
acids
• Tertiary – 3D folding of the polypeptide
• Quaternary – arrangements of multiple polypeptides
16. Levels of Structure
• Primary structure: the sequence of amino
acids
• Secondary structure: conformations of amino
acids in localized regions of a polypeptide
chain; examples are α-helix, β-pleated sheet,
and random coil.
• Tertiary structure: the complete threedimensional arrangement of atoms of a
polypeptide chain.
• Quaternary structure: the spatial relationship
and interactions between subunits in a protein
that has more than one polypeptide chain.
17. 1) Primary Structure
• the sequence of amino acids in a polypeptide
chain.
• The number peptides possible from the 20
protein-derived amino acids is enormous.
– the number of peptides possible for a chain of n
amino acids is 20n.
– for a small protein of 60 amino acids, the number
of proteins possible is 2060 = 1078
18. Primary Structure
• The hormone
insulin consists of
two polypeptide
chains held
together by two
interchain disulfide
bonds.
19. Primary Structure
• Just how important is the exact amino acid
sequence?
– Human insulin consists of two polypeptide chains
having a total of 51 amino acids.
– In the table are differences between four types of
insulin.
A Chain
p ositions 8-9-10
B Chain
p osition 30
H uman
Cow
-Thr-Ser-Ile-A la-Ser-Val-
-Thr
-Ala
H og
-Thr-Ser-Ile-
-Ala
Sh eep
-Ala-G ly-Val-
-Ala
20. Primary Structure
– Vasopressin and oxytocin are both nonapeptides
but have quite different biological functions.
– Vasopressin is an antidiuretic hormone.
– Oxytocin affects contractions of the uterus in
childbirth and the muscles of the breast that aid in
the secretion of milk.
22. 2) Secondary Structure
• conformations of amino acids in localized
regions of a polypeptide chain.
– The most common types of secondary structure
are α-helix and β-pleated sheet.
α-Helix: a type of secondary structure in which a
section of polypeptide chain coils into a spiral,
most commonly a right-handed spiral.
β-Pleated sheet: a type of secondary structure in
which two polypeptide chains or sections of the
same polypeptide chain align parallel to each other
24. α-Helix
• In a section of α-helix;
– The C=O group of
each peptide bond is
hydrogen bonded to
the N-H group of the
peptide bond four
amino acid units away
from it.
– All R- groups point
outward from the helix.
25. secondary structure
• Note the position of the
purple R groups relative
to the backbone of the
polypeptide
26. all α helices are right handed
• But some
supramolecular
complexes are
left handed
(keratin,
collagen)
right-handed = clockwise
27. β sheet secondary structure
• More extended
• H-bonds may occur between amino acids some
distance from one another
• Adjacent chains can run parallel or anti-parallel
to each other
28. β-Pleated Sheet
• In a section of β-pleated sheet;
– The C=O and N-H groups of peptide bonds from
adjacent chains point toward each other so that
hydrogen bonding is possible between them.
– All R- groups on any one chain alternate, first
above, then below the plane of the sheet, etc.
31. 3) Tertiary Structure
• the overall conformation of an entire
polypeptide chain.
• Tertiary structure is stabilized in four ways:
– Covalent bonds, as for example, the formation of disulfide
bonds
bonds between cysteine side chains.
– Hydrogen bonding between polar groups of side chains, as
for example between the -OH groups of serine and
threonine.
– Salt bridges, as for example, the attraction of the -NH3+
bridges
group of lysine and the -COO- group of aspartic acid.
– Hydrophobic interactions, as for example, between the
interactions
nonpolar side chains of phenylalanine and isoleucine.
32. Cysteine
• The -SH (sulfhydryl) group of cysteine is easily
oxidized to an -S-S- (disulfide).
35. Tertiary Structures of Proteins
• the three dimensional shape of proteins that results
from further crosslinking, folding and interaction
between R groups
1) disulfide linkages (-S-S-) b/w cysteins
2) dipole dipole interactions b/w polar groups
3) hydrogen bonding on side chains
4) London forces
36. relative compactness of proteins
• Hypothetical chain length of a protein if it were to
appear either as an α helix or β sheet
37. 4) Quaternary Structure
• the arrangement of polypeptide chains into a
noncovalently bonded aggregation.
– The individual chains are held together by
hydrogen bonds, salt bridges, and hydrophobic
interactions.
• Hemoglobin
– Adult hemoglobin: two chains of 141 amino acids
each, and two chains of 146 amino acids each.
– Each chain surrounds an iron-containing heme
unit.
39. Denaturation
• the process of destroying the native
conformation of a protein by chemical or
physical means.
– Some denaturations are reversible, while others
permanently damage the protein.
40.
41. Protein Function
• Protein function often includes reversible
binding interactions with other molecules.
• Complementary interactions between
proteins and ligands are the basis of self vs
non-self recognition by the immune system.
• Specific protein interactions modulated by
chemical energy are the basis of muscle
movement.
44. Hemoglobin
Binds O2 is a cooperative process.
Binding affinity of Hb for O2 is increased by the O2
saturation of the molecule
with the first O2 bound influencing the shape of the
binding sites (conformation change) for the next O2
45. hemoglobin-O2 binding allosterically
modulated by 2,3-bisphosphoglycerate
BPG reduces the affinity of
Hb for O2.
BPG binds at a site distant
from the O2-binding site
and regulates the affinity of
Hb for O2.
46. immune responses are mediated by protein
interactions that distinguish self and non-self
Cellular immune response - T cells destroy host
cells infected by viruses
Humoral immune response – B cells produce
antibodies or immunoglobulins against bacteria,
viruses and foreign molecules
47. muscle contraction is also based on protein
interactions and conformational changes
Muscle contraction occurs by the
sliding of the thick (myosin) and thin
(actin) filaments past each other
Conformational
changes in the
myosin head
are coupled to
ATP hydrolysis
http://www.sci.sdsu.edu/movies/
48. 1. What 2 functional groups are present in all amino acids?
2. Name the simplest amino acid. Is it a chiral molecule?
3. Approximately how many amino acids are needed to make
the proteins found in the body?
4. What element is present in proteins but not in sugars or
fats?
49. 5. What is meant by the primary, secondary and tertiary
structures of proteins?
6. What type of bonds are responsible for the helix structure
of some proteins?
Notas del editor
FIGURE 5-1 Heme. The heme group is present in myoglobin, hemoglobin, and many other proteins, designated heme proteins. Heme consists of a complex organic ring structure, protoporphyrin IX, with a bound iron atom in its ferrous (Fe2+) state. (a) Porphyrins, of which protoporphyrin IX is only one example, consist of four pyrrole rings linked by methene bridges, with substitutions at one or more of the positions denoted X. (b, c) Two representations of heme (derived from PDB ID 1CCR). The iron atom of heme has six coordination bonds: four in the plane of, and bonded to, the flat porphyrin ring system, and (d) two perpendicular to it.
FIGURE 5-6 Comparison of the structures of myoglobin (PDB ID 1MBO) and the β subunit of hemoglobin (derived from PDB ID 1HGA).
FIGURE 5-12 A sigmoid (cooperative) binding curve. A sigmoid binding curve can be viewed as a hybrid curve reflecting a transition from a low-affinity to a high-affinity state. Because of its cooperative binding, as manifested by a sigmoid binding curve, hemoglobin is more sensitive to the small differences in O2 concentration between the tissues and the lungs, allowing it to bind oxygen in the lungs (where pO2 is high) and release it in the tissues (where pO2 is low).
FIGURE 5-16 Effect of pH on oxygen binding to hemoglobin. The pH of blood is 7.6 in the lungs and 7.2 in the tissues. Experimental measurements on hemoglobin binding are often performed at pH 7.4.
FIGURE 5-17 Effect of BPG on oxygen binding to hemoglobin. The BPG concentration in normal human blood is about 5 mM at sea level and about 8 mM at high altitudes. Note that hemoglobin binds to oxygen quite tightly when BPG is entirely absent, and the binding curve seems to be hyperbolic. In reality, the measured Hill coefficient for O2-binding cooperativity decreases only slightly (from 3 to about 2.5) when BPG is removed from hemoglobin, but the rising part of the sigmoid curve is confined to a very small region close to the origin. At sea level, hemoglobin is nearly saturated with O2 in the lungs, but just over 60% saturated in the tissues, so the amount of O2 released in the tissues is about 38% of the maximum that can be carried in the blood. At high altitudes, O2 delivery declines by about one-fourth, to 30% of maximum. An increase in BPG concentration, however, decreases the affinity of hemoglobin for O2, so approximately 37% of what can be carried is again delivered to the tissues.
FIGURE 5-30 Muscle contraction. Thick filaments are bipolar structures created by the association of many myosin molecules. (a) Muscle contraction occurs by the sliding of the thick and thin filaments past each other so that the Z disks in neighboring I bands draw closer together. (b) The thick and thin filaments are interleaved such that each thick filament is surrounded by six thin filaments.
FIGURE 5-31 Molecular mechanism of muscle contraction. Conformational changes in the myosin head that are coupled to stages in the ATP hydrolytic cycle cause myosin to successively dissociate from one actin subunit, then associate with another farther along the actin filament. In this way the myosin heads slide along the thin filaments, drawing the thick filament array into the thin filament array (see Figure 5-30).
