Transcript video slide

The Structure and
Function of
Macromolecules
Chapter 5
3 -- Proteins
Macromolecules:
The Molecules of Life
 Carbohydrates
 Nucleic Acids
 Proteins
 Lipids
2
Proteins
 Polypeptides -- polymers of amino acids
 Protein -- one or more polypeptides
 Proteins -- many structures with wide range of functions
 Proteins -- more than 50% of the dry mass of most
cells
 Proteins -- include structural support, storage,
transport, cellular communications, movement, and
defense against foreign substances
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4
Amino Acid Monomers
 Organic molecules with carboxyl and amino groups
 Different properties due to differing side chains,
called R groups
 20 amino acids to make thousands of proteins
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LE 5-UN78
a carbon
Amino
group
Carboxyl
group
LE 5-17a
Glycine (Gly)
Alanine (Ala)
Valine (Val)
Leucine (Leu)
Isoleucine (Ile)
Nonpolar
Methionine (Met)
Phenylalanine (Phe)
Tryptophan (Trp)
Proline (Pro)
LE 5-17b
Polar
Serine (Ser)
Threonine (Thr)
Cysteine (Cys)
Tyrosine (Tyr)
Asparagine (Asn) Glutamine (Gln)
LE 5-17c
Acidic
Basic
Electrically
charged
Aspartic acid (Asp) Glutamic acid (Glu)
Lysine (Lys)
Arginine (Arg)
Histidine (His)
Amino Acid Polymers
 Amino acids -- linked by peptide bonds
 A polypeptide -- polymer of amino acids
 Polypeptide length -- few monomers to more than a
thousand
 Each polypeptide has a unique linear sequence of
amino acids
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Determining the Amino Acid
Sequence of a Polypeptide
 First determined by chemical methods
 Now? Mostly automated – DNA sequencer
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LE 5-20a
Amino end
Primary structure
Amino acid
subunits
unique sequence of
amino acids
Carboxyl end
LE 5-20b
Secondary structure
 Interactions between backbone components

Hydrogen bonds

Typical secondary structures are coils (alpha helix) and a folded
structure (beta pleated sheet)
b pleated sheet
Amino acid
subunits
a helix
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Tertiary Structure
LE 5-20d
Interactions between
R groups
 Include
hydrogen
bonds, ionic bonds,
hydrophobic
interactions, and van
der Waals interactions
 Disulfide bridges may
reinforce the protein’s
conformation
Hydrophobic
interactions and
van der Waals
interactions
Polypeptide
backbone
Hydrogen
bond
Disulfide bridge
Ionic bond
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Four Levels of Protein Structure
 Primary structure -- unique sequence of amino
acids
 Secondary structure – interactions between
backbone components
 Tertiary structure -- interactions between
various side chains (R groups)
 Quaternary structure – proteins consisting of
multiple polypeptide chains
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Proteins with Quaternary Structure
 Collagen is a fibrous protein consisting of three
polypeptides coiled like a rope
 Hemoglobin is a globular protein consisting of
four polypeptides: two alpha and two beta
chains
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Sickle-Cell Disease: A Simple
Change in Primary Structure
 A slight change in primary structure can affect a
protein’s conformation and ability to function
 Sickle-cell disease, an inherited blood disorder,
results from a single amino acid substitution in the
protein hemoglobin
10 µm
Red blood Normal cells are
cell shape full of individual
hemoglobin
molecules, each
carrying oxygen.
10 µm
Red blood
cell shape
Fibers of abnormal
hemoglobin deform
cell into sickle
shape.
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LE 5-21b
Sickle-cell hemoglobin
Normal hemoglobin
Primary
structure
Val
His
1
2
Leu
Thr
3
4
Pro
Glu
5
6
Secondary
and tertiary
structures
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b subunit
Quaternary Normal
hemoglobin
structure
(top view)
Primary
structure
Secondary
and tertiary
structures
Molecules do
not associate
with one
another; each
carries oxygen.
His
Leu
Thr
Pro
Val
Glu
1
2
3
4
5
6
7
Exposed
hydrophobic
region
b subunit
a
Quaternary
structure
b
Val
b
a
Function
Glu
Sickle-cell
hemoglobin
b
a
Function
Molecules
interact with
one another to
crystallize into
a fiber; capacity
to carry oxygen
is greatly reduced.
b
a
LE 5-19
Groove
A ribbon model
Groove
A space-filling model
Conformation and Function
 Conformation – 3-D shape
 Functional protein -- one or more polypeptides
twisted, folded, and coiled into a unique shape
 Sequence -- determines a protein’s threedimensional conformation
 Conformation -- determines its function
 Ribbon models and space-filling models can
depict a protein’s conformation
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What Determines Protein
Conformation?
 In addition to primary structure, physical and
chemical conditions can affect conformation
 Alternations in pH, salt concentration, temperature,
or other environmental factors can cause a protein to
unravel
 This loss of a protein’s native conformation is called
denaturation
 A denatured protein is biologically inactive
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LE 5-22
Denaturation
Normal protein
Denatured protein
Renaturation
The Protein-Folding Problem
 Prediction of conformation is non-trivial
 Thousands of possible conformations!
 Most proteins probably go through several states on
their way to a stable conformation
 Chaperonins assist the proper folding of other
proteins
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LE 5-23a
Cap
Hollow
cylinder
Chaperonin
(fully assembled)
LE 5-23b
Polypeptide
Steps of Chaperonin
Action:
An unfolded polypeptide enters the
cylinder from one
end.
Correctly
folded
protein
The cap attaches, causing
the cylinder to change
shape in such a way that
it creates a hydrophilic
environment for the
folding of the polypeptide.
The cap comes
off, and the
properly folded
protein is released.
 Scientists use X-ray crystallography to determine a
protein’s conformation
 Another method is nuclear magnetic resonance
(NMR) spectroscopy, which does not require
protein crystallization
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X-ray diffraction pattern
3D computer model
The Flow of Genetic Information
 The information content -- DNA sequence
 DNA – directs synthesis of proteins
 Gene manufacture
 Transcription
 Translation
 Ribosome -- where translation happens
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LE 17-4
Gene 2
DNA
molecule
Gene 1
Gene 3
DNA strand
(template)
5
3
TRANSCRIPTION
mRNA
5
3
Codon
TRANSLATION
Protein
Amino acid
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Nutritional Mutants in Neurospora
 Beadle and Tatum – irradiated mold resulting in
inability to synthesize certain molecules
Three classes of arginine-deficient mutants
 3 different enzymes necessary for synthesizing arginine

 “One gene–one enzyme” hypothesis
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The Products of Gene Expression:
A Developing Story
 Not all proteins are enzymes!
 One gene–one protein
 Quaternary structure -- each component needs its
own gene

ATP synthase has 16 subunits!
 Now -- Beadle and Tatum’s hypothesis “one
gene–one polypeptide”
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Basic Principles of Transcription
and Translation
 Transcription -- synthesis of RNA under the
direction of DNA
produces messenger RNA (mRNA)
 “language” of DNA to “language” of RNA

 Translation -- synthesis of a polypeptide under the
direction of mRNA

Ribosomes are the sites of translation

“language” of Nucleic Acids to “language” of Amino Acids
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LE 17-4
Gene 2
DNA
molecule
Gene 1
Gene 3
DNA strand
(template)
5
3
TRANSCRIPTION
mRNA
5
3
Codon
TRANSLATION
Protein
Amino acid
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DNA to RNA
 DNA in eukaryotes is in the nucleus
 Protein synthesis occurs at ribosomes in the
cytoplasm
 DNA information -- from nucleus to cytoplasm

intermediary (RNA)
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RNA Intermediaries
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 A ribosome has three
binding sites for tRNA:
P site -- holds the
tRNA
 The A site -- holds the
tRNA with next amino
acid
 The E site -- exit site,
where discharged
tRNAs leave the
ribosome

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