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Chapter 4

Protein Structure and Function


Essential
Cell Biology
Third Edition
Copyright Garland Science 2010
Structure Protein: Provides the cell with shape and structure (tubulin and
actin)
Enzymes: Catalyze covalent bond breakage or formation (pepsin)
Transport Protein: Carries other molecules or ions (hemoglobin oxygen)
Motor Protein: Generates movement in cells and tissues (Myosin)
Storage Protein: Stores small molecules or ions (ferritin - iron in liver)
Signal Protein: Carries signals from cell to cell (insulin glucose levels)
Receptor Protein: Detects signals and transmits them to the
cells response machinery (insulin receptor)
Gene Regulatory Protein: Binds to DNA to switch genes on or
off (transcriptional factors lactose repressor)
A few examples of some general protein functions
(I)
The shape and structure of proteins
Figure 4-1 Essential Cell Biology (Garland Science 2010)
Amino acids are linked together by peptide bonds
Oxygen
Carboxyl group
Amino group
Hydrogen
Nitrogen
Carbon
Figure 4-2 Essential Cell Biology (Garland Science 2010)
A Protein is made of amino acids linked
together into a polypeptide chain
Figure 4-3 Essential Cell Biology (Garland Science 2010)
Twenty different amino acids are linked
together by peptide bonds
Types of noncovalent bonds or interactions
help proteins fold
hydrogen bonds: When a hydrogen atom is sandwiched
between electron-attracting atoms (oxygen or nitrogen).
electrostatic attractions: between charged groups.
van der Waals attractions: attractions between two atoms
at very short distances.
Hydrophobic interaction
Three types of noncovalent bonds
Figure 4-4 Essential Cell Biology (Garland Science 2010)
Three types of non-covalent bonds help protein fold
Figure 4-5 Essential Cell Biology (Garland Science 2010)
Hydrophobic forces help proteins fold into
compact conformations
Figure 4-6 Essential Cell Biology (Garland Science 2010)
Hydrogen bonds within a protein molecule help
stabilize its folded shape
Figure 4-7 Essential Cell Biology (Garland Science 2010)
Denatured proteins can recovered their natural shapes
to maintain a conformation of lowest energy
Figure 4-8 Essential Cell Biology (Garland Science 2010)
Prion diseases are caused by rare proteins
whose misfolding is infectious
Dr. Stanley Prusiner
Nobel Prize in Medicine 1997
Discovery of Prions - a new
biological principle of infection" .
Figure 4-9 Essential Cell Biology (Garland Science 2010)
Protein come in a variety of shapes and sizes
100 amino acids
3-D structure
A ribbon model
helices and sheets
The helix is a common folding pattern of proteins
The N-H of every peptide bond is hydrogen-bonded to the C=O of a neighboring
peptide bond located four amino acids away in the same chain
The helix is a common folding pattern
The sheet is a common folding pattern of proteins
The individual strands in the sheet are held together by hydrogen-bonding
between peptide bonds in different strands, and side chains in each strand
project alternately above and below the plane of the sheet
Figure 4-11 Essential Cell Biology (Garland Science 2010)
The helix is a regular biological structure
Movie: The helix
Figure 4-12 Essential Cell Biology (Garland Science 2010)
A segment of helix can cross a lipid bilayer
Hydrophobic hydrocarbon
tails of phospholipid
Intertwined helices can form a coiled-coil
Nonpolar side chains
Figure 4-14 Essential Cell Biology (Garland Science 2010)
Sheet come in two varieties:
Parallel and Antiparallel
Pauling and Corey
proposed the
structures of
helix and sheet.
Linus Pauling won the
Nobel Prize in
Chemistry 1954
Figure 4-16 Essential Cell Biology (Garland Science 2010)
Many proteins are composed of
separate functional domains
Figure 4-17 Essential Cell Biology (Garland Science 2010)
Ribbon models show three different protein domains
Figure 4-18 Essential Cell Biology (Garland Science 2010)
Serine proteases comprise a family of
proteolytic enzymes
Identical amino acid sequence
Active site:
serine
Figure 4-19 Essential Cell Biology (Garland Science 2010)
Many protein molecules contain multiple copies of
a single protein subunit
Figure 4-20 Essential Cell Biology (Garland Science 2010)
Some proteins contain two different subunits
Hemoglobin contains two copies of -globin and two copies of -globin
A heme molecule
can bind one O2
Figure 4-21 Essential Cell Biology (Garland Science 2010)
Protein can assemble into complex structures
Figure 4-22 Essential Cell Biology (Garland Science 2010)
An actin filament is composed of
identical protein subunits
Figure 4-23 Essential Cell Biology (Garland Science 2010)
Single protein subunits can pack to form
a filament, tube, or a spherical shell
Figure 4-25a Essential Cell Biology (Garland Science 2010)
Collagen is a triple helix formed by three protein
chains that wrap around one another
Cross-linked
Figure 4-26 Essential Cell Biology (Garland Science 2010)
Disulfide bonds help stabilize a favored
protein conformation
(II)
How proteins work
Figure 4-27 Essential Cell Biology (Garland Science 2010)
The binding of a protein to another molecule
is highly selective
Figure 4-28a Essential Cell Biology (Garland Science 2010)
The folding of the polypeptide chain creates
a cavity on the protein surface
Figure 4-28 Essential Cell Biology (Garland Science 2010)
Binding site allow a protein to interact
with specific ligands
Figure 4-29 Essential Cell Biology (Garland Science 2010)
An antibody is Y-shaped and has two identical
binding sites for its antigen
Table 4-1 Essential Cell Biology (Garland Science 2010)
Some common functional classes of enzymes
Figure 4-30 Essential Cell Biology (Garland Science 2010)
Lysozyme cleaves a polysaccharide chain
S: substrate, E: enzyme, P: product
The lysozyme cuts the polysaccharide by catalyzing
the addition of a water molecule to one of the
sugar-sugar bonds.
Figure 4-31 Essential Cell Biology (Garland Science 2010)
In the active site of lysozyme, bonds
are bent and broken
Movie: Lysozyme cleaves a polysaccharide chain
Figure 4-32 Essential Cell Biology (Garland Science 2010)
Enzymes can encourage catalysis in several ways
(III)
How proteins are controlled
Figure 4-34 Essential Cell Biology (Garland Science 2010)
Feedback inhibition regulates the flow through
biosynthetic pathways
B is the first metabolite in a
pathway that gives the end
product Z. Z inhibits the first
enzyme for its synthesis and
thereby controls its own
concentration in the cell.
Figure 4-36 Essential Cell Biology (Garland Science 2010)
Feedback inhibition triggers a conformational change
The multisubunit enzyme, aspartate transcarbamoylase,
catalyzes an important reaction that begins the synthesis of
the pyrimidine ring of C, U, and T nucleotide. One of final
products of this pathway, cytosine triphosphate (CTP), binds
to the enzyme to turn it off whenever CTP is plentiful.
Figure 4-37 Essential Cell Biology (Garland Science 2010)
An increase of ligand (ADP) concentration activates
the enzymatic reaction for oxidation of sugars
ADP can bind only to the enzyme in its closed conformation
and thereby lowers the energy of the closed conformation,
locking nearly all of the enzymes in the active form.
Figure 4-38a Essential Cell Biology (Garland Science 2010)
Protein phosphorylation is a very common mean
of regulating protein activity
Figure 4-38b Essential Cell Biology (Garland Science 2010)
Protein phosphorylation is a very common means
of regulating protein activity
Figure 4-39 Essential Cell Biology (Garland Science 2010)
GTP-binding proteins form molecular switches
Figure 4-40 Essential Cell Biology (Garland Science 2010)
A large conformational change is produced in EF-Tu
in response to nucleotide hydrolysis
The GTP-binding protein EF-Tu binds tRNA on the ribosome and
plays a role in the elongation of a polypeptide chain during protein
synthesis. In its GTP-bound form, EF-Tu binds a tRNA molecule
tightly. The hydrolysis of bound GTP causes a large conformational
changes within the protein and leads to release of the tRNA.
An allosteric mortor protein, driven by ATP
hydrolysis, moves in one direction
An orderly transition
among three
conformations is driven
by the hydrolysis of a
bound ATP molecule. By
repeated cycles of the
conformation changes,
the protein moves
continuously to the right
along the thread.
Figure 4-44a Essential Cell Biology (Garland Science 2010)
The modification of a protein at multiple site produce
a regulatory code that controls the protein behavior
Acetylation Ubiquitylation
Phosphorylation
Figure 4-44b Essential Cell Biology (Garland Science 2010)
Some of the covalent modifications that control
the activity and degradation of the protein p53
Acetylation
Ubiquitylation
Phosphorylation
(IV)
How proteins are studied
Figure 4-45 (part 1 of 2) Essential Cell Biology (Garland Science 2010)
Mass spectrometry can be used to identify proteins
by determine the precise masses of peptides
Two-dimensional
electrophoresis
Figure 4-45 (part 2 of 2) Essential Cell Biology (Garland Science 2010)
Mass spectrometry can be used to identify proteins
by determine the precise masses of peptides
Figure 4-46 Essential Cell Biology (Garland Science 2010)
The structure of a protein can be determined
by X-ray crystallography
Figure 4-48 Essential Cell Biology (Garland Science 2010)
Cells in culture often display properties
that reflect their origin
Fibroblasts
Oligodendrocytes
(Neurons)
Myoblasts
Epithelial cells
Tobacco cells
Affinity chromatography can be used to isolate the
binding partners of a protein of interest