Transcript Chapt. 3-Proteins - University of New England

Chapt. 3-Proteins
pgs. 36-42
• Make up ~50 dry weight of
any organism.
• Roles:
– Enzymes. Assist in
chemical reactions
– Defense. Immune system
– Structural roles:
Keratin
Muscles
Cytoskeleton
- Chemical messengers.
Hormones
Proteins: Made up of
Amino Acids
• All proteins have a similar basic structure.
They are all composed of small units called
amino acids (AA).
• Stick a bunch of AA together and make a
protein.
• So what’s an amino acid?
Amino Acids
• A molecule composed of 4
pieces all covalently bonded
to a central C atom:
1. An amino group (NH2)
2. A carboxyl group (COOH)
3. An H atom
4. An R group
• Text pg. 36-37
• If it has these 4 traits, it’s an
AA!!
Amino Acids
• There are 20 common AA
used in making proteins in
living organisms
• R groups account for the
differences:
R may be small- CH3
OR, R may be a large aromatic
ring
• R groups define the behavior
of an AA
• Text pg 37
R Groups in AA
• Nonpolar R groups: -CH3 or -CH2
• Polar-Uncharged R groups: usually with an
-OH or =O
• Polar-Charged R groups: posses acidic (-) or
basic (+) groups such as -COOH or -NH
• Aromatic R groups: contain a carbon ring
• Text pg. 37
R Groups in AA define the
protein structure & function
• The chemical behavior
of a protein is
determined by the AA
properties…
• Whether the AA are
polar or charged or
aromatic.
How to make a protein?
• Proteins are simply
chains of AA stuck
together
• 2 AA link together via
a peptide bond to form
a polypeptide
• Add many AA in this
fashion to form a
protein
Peptide Links
• Covalent bonds
between the COOH of one AA
and the -NH2 on
another
• Text pg. 38
• Numerous peptide
links will form
longer and longer
polypeptides
Quiz
• How many different Amino acids are there?
• How do we link together 2 AA ?
• How can we form different types of
proteins?
Protein Structure
• Proteins rarely exist as long straight chains of AA
AA1-AA2-AA3-AA4-AA5-AA6
• Functional proteins are more commonly formed
into folded, globular structures
• Text pg. 39
Levels of Protein Structure
• Primary (10) Structure: The AA linear
sequence. The chain of AA...
Ala-Gly-Ser-Val-Thr
• Text pg. 39
Protein Structure
• 20 Structure: Hydrogen bonding may occur
between different AA in the same chain …
– Leading to a coiled alpha (a) helix structure….
• OR, Hydrogen bonding may occur between
different AA in neighboring chains.
– Leading to a pleated sheet (b) structure.
• Text pg. 39
Protein 20 Folding
a-Helix
• The alpha helix resembles
a ribbon of amino acids
wrapped around a tube to
form a stair case like
structure. Here is pictured
a ribbon and ball and stick
diagram of a model alpha
helix. This structure is
very stable, yet flexible
and is often seen in parts
of a protein that may need
to bend or move.
Protein 20 Folding
b-Sheet
In the beta sheet, two planes of
amino acids will form, lining up
in such a fashion so that
hydrogen bonds can form
between facing amino acids in
each sheet. The beta pleated sheet
or beta sheet is different than the
alpha helix in that far distant
amino acids in the protein can
come togeher to form this
structure. Also, the structure
tends to be rigid and less flexible.
Motifs
• Supersecondary
protein structures
in which multiple a
helices and b sheets
combine to form
complex,
characteristic folds.
• example: a b a
Supersecondary Protein Structures
2 Transmembrane proteins
Domains
• Definite 3D regions along a polypeptide with
a precise function
• Example: enzyme binding sites, substrate
binding sites
Protein Structure
• Tertiary (30) Structure:
The tightly folded
structure in which
motifs and
polar/nonpolar groups
all take on a 3D shape.
• Text pg 40
Protein Structure
• Quaternary (40)
Structure: Several 30
polypeptide chains
link together to form
complete multisubunit protein
• I.e. Hemoglobin is
composed of 4
separate chains
• Text pg. 39, 41
Protein Folding
An Analogy
30
20
10
How do Proteins fold correctly?
• As proteins are produced, they may take on
any number of different shapes…but only
one is correct.
• Other proteins, termed Chaperones, help in
the correct folding process
Molecular Chaperones
• Molecular chaperones are proteins that are grouped together
into highly conserved families. By binding to incompletelyfolded target proteins, molecular chaperones help them to
complete folding, assemble into correct structures, or
translocate across an intracellular membranes.
• Therefore, molecular chaperones play pivotal roles in normal
protein metabolism in an environment that is so densely
packed with macromolecules that unchaperoned processes are
virtually impossible.
• Under suboptimal conditions, such as encountered when
applying mild heat to cells, the proteins will misfold and
aggregate. Cells respond to such stress by increasing the
expression of a subset of genes encoding the so-called heat
shock proteins. Not surprisingly the majority of heat shock
proteins are molecular chaperones.
Heat Shock
leads to Unfolding Proteins
• When proteins are exposed to dramatic
environmental changes, they will unfold.
• A term for unfolded proteins is denatured
proteins
• If we cook or change pH or salt levels, we
denature proteins.
When yeast cells are given a mild heat shock, some proteins unfold and aggregate,
such as the molecular chaperone (Hsp104). We investigated the subcellular
distribution of Hsp104 in normal and heat shocked cells. Hsp104 relocalizes in
response to heat shock into irregular foci that disappear upon recovery at optimal
temperatures. We have tagged Hsp104 with a fluorescent protein (GFP) so that its
subcellular responses to various physiological conditions can be observed.
A) After mild heat shock, Hsp104 redistributes into irregularlyshaped foci, presumably aggregates of heat-damaged protein.
B) After 1h recovery, Hsp104 is again uniformly distributed.
http://bioinfo.med.utoronto.ca/Brochure/JG.html
Nucleic Acids
• Information storage
molecules
• Cells receive
instructions from
nucleic acids about
which proteins to
make
• Nucleic acids come in
two types:
DNA
RNA
DNA/RNA Structure
• Both similar…composed of a long sequence
of small molecules..
• Termed nucleotides.
• Many small nucleotides linked together
form a large DNA or RNA macromolecule.
Nucleotides
• Composed of
only 3 parts:
1) 5C sugar
2) Phosphate group
3) Ring-shaped
Nitrogen base
• Text pg. 47
3
2
1
Nucleotides build
Nucleic Acids
• Individual nucleotides
link together by the PO4
of one linking to the
sugar of another.
• This linkage is a
dehydration reaction...
• And is termed a
phosphodiester linkage
http://krupp.wcc.hawaii.edu/BIOL100/present/molegene/sld008.htm
Nucleotides contain information.
How?
• Of the 3 ingredients in a nucleotide, only the
N-bases show any real variety
• It is these N-bases that account for all the
information in living organisms
• And yet, there are only 5 different types of Nbases…..
Nitrogen-Bases
Adenine
Guanine
Cytosine
Thymine
Uracil
Uracil
Just 5 different N-bases
determine all of life on earth!
2 Types of Nucleic Acid:
RNA & DNA
• Differ in a few essential ways:
• Text pg. 48
DNA
• Exists as long double
linear sequence
• Two long polymers of
DNA wind around each
other to form a helical
structure
• Termed a double helix…a
twisted ladder
• The two strands run in
opposite directions…..
they are antiparallel
DNA
Uses A,T,C & G bases only
Text pg 47
DNA
• The 5-C sugar in DNA
is ribose with one
missing O atom on
Carbon #2
• = deoxy-ribose
What holds DNA antiparallel
strands together??
• H-bonds between nitrogen
bases on opposite strands
• There is room between DNA
strands for 3 carbon ring
structures…
• So… purines (A,G) align
with pyrimidines (C, T) in a
precise way
• This is known
as..Complementary pairing
• A-T and C-G always pair up
• Text pg. 47
RNA
• Usually singlestranded
• Uses Uracil as a
substitute for Thymine
• RNA uses U,A,G & C
RNA
• Sugar component is
5C Ribose
• Ribose has an -OH
group on Carbon #2
The Central Dogma
of Biology
• DNA makes RNA makes Protein
• DNA --> RNA --> Protein