Molecules with Diverse

Structures and Functions

Major constituent of most cells (>50% dry weight)
Highly sophisticated molecules (or multi-molecular
complexes)
Extremely large number of unique proteins exist
They are polymers folded into specific conformations
(shapes)
Proteins define what an organism is, what it looks like,
how it behaves, etc. (responsible for most phenotype)
A. Diverse Functions:
1. Enzyme catalysis
a. Facilitate biological reactions
b. Globular, three-dimensional shape
2. Defense
a. Antibodies recognize foreign cells
3. Transport
a. Globular proteins that transport small molecules, hormones, ions and gases
b. Examples: hemoglobin, transferrin, albumin
4. Act as buffers
5. Maintain fluid and electrolyte balance
6. Support
a. Fibrous proteins are structural
b. Include keratin, collagen, and fibrin
c. Most abundant protein in vertebrates
7. Motion
a. Muscle contraction due to sliding of actin and myosin filaments
b. Contractile proteins in cytoskeleton
8. Receptor proteins
a. Receptors on membrane of nerve cells that detect chemical signals that are
released by other nerve cells
9. Storage
a. Storage for amino acids
b. Stores ions, such as ferritin (stores iron)
10. Hormonal proteins
11. Regulation, through;
a. Hormones, which are intercellular messengers
b. Cell surface receptors receive information
A. Complex, Versatile Molecules
1. Polymers of only 20 amino acids
2. Among the first biological molecules to evolve
B. Amino Acid structure
1. Amino, carboxyl and hydrogen bonded to a central carbon
2. Identification conferred by a variable R group
3. Classified into five classes according to the R group

The chemistry of R
groups distinguishes
amino acids and their
a. Nonpolar properties
- example: leucine
- often contain –CH2, --CH3, or only --H
b. Polar, uncharged
1. Example: threonine
2. Contain oxygen
c. Ionizable
1. Example: glutamic acid
2. Contain acids or bases
d. Aromatic
1. Example: phenylalanine
2. Contain organic ring with alternating single and double bonds
e. Special function
1. Example: methionine, proline, cysteine
2. Confer unique individual properties
C. Proteins are polymers of amino acids
1. Ionized amino acids as amino (NH3+) on one end, carboxyl (COO-) on the other
2. Amino acids are linked together by peptide bonds
a. Condensation reaction between amino and carboxyl ends
b. Lose water molecule, form covalent bond
c. Bond is stiff, molecules can’t rotate
3. Proteins are composed of one or more polypeptides
4. Polypeptides are long chains of amino acids
5. Each protein has a unique, defined amino acid sequence
6. 20 common amino acids with characteristic side groups
A. Overview of protein structure
1. Proteins are amino acid chains folded into complex
shapes
2. Examine three dimensional structures with X-ray
diffraction
a. Myoglobin was the first one examined
b. All internal amino acids are nonpolar
c. Hydrophobic interactions shove nonopolar molecules inside
d. Polar and charged amino acids are usually on the surface of
proteins
B. Levels of protein structure
1. Possess structural levels
a. Four initial levels: primary, secondary, tertiary and
quaternary structures
2. Primary structure
a. Specific amino acid sequence is determined by gene’s
nucleotide sequence
b. Permits great diversity of proteins
1’ structure =
ordered
sequence of
amino acids
Note the Note also the disulfide
Polarity of linkages (cys-cys  S-
the S bonds; actually
sequence considered a component
(amino  of tertiary structure)
carboxy)
3. Secondary structure
a. Proteins have segments of their polypeptide chain
repeatedly coiled or folded in a pattern that contribute
to the protein’s overall conformation
b. Secondary structures are the result of hydrogen bonds
at regular intervals along the polypeptide backbone
c. --COOH and –NH groups of main chain form
hydrogen bonds
d. Two pattern of H bonding
1. Linking of two amino acids along chain forms α helix
2. Many parallel links across two chains form β pleated sheet
Held together by interactions (H-
bonds) between peptide backbones
4. Tertiary structure
a. Protein’s final folded shape, positions motifs and
side groups
b. Initially driven by hydrophobic interactions with
water
c. Interactions between the R group of the various
amino acids will lead to the final folded shape of the
globular protein
d. Allow very close fitting of nonpolar chains in
protein interior
e. A single amino acid change can significantly
disrupt fit
The Tertiary structure is stabilized by a number of forces:
1. Hydrogen bonding between R groups of the
different amino acids
2. Electrostatic attraction between R groups
3. Hydrophobic exclusion of nonpolar R groups
4. Disulfide covalent bonds
Tertiary structure is controlled
by the interactions between
non-adjacent amino acid R
groups (note bond types)
5. Quaternary structure
a. Combination of two or more polypeptide
subunits
b. Composes functional unit of a protein
c. Change in one amino acid can have
profound effect, such as in Sickle cell
anemia
Quaternary structure is the
interaction between adjacent
polypeptides that make up a single
protein

Note that the polypeptides reside in

discrete subunits rather than being
tangled together like spaghetti
“’Polypeptide’ is not quite
synonymous with
‘protein.’ The relationship
is somewhat analogous
to that between a long
strand of yarn and a
sweater of a particular
size and shape that one
can knit from the yarn. A
functional protein is not
just a polypeptide chain,
but one or more
polypeptides precisely
twisted, folded, and
coiled into a molecule of
unique shape. It is the
amino-acid sequence of
a polypeptide that
determines what three-
dimensional
conformation the protein
will take.”
A. Nonpolar proteins play key role in protein folding
1. Folding is not a simple hydrophobic interaction
2. It is important for proteins to fold, because they have sticky interior
portions, and if they were unfolded they might stick to other proteins
3. This is prevented by chaperone proteins
B. Chaperonins
1. Special proteins that help new proteins fold correctly
a. Identified and studied extensively in E. coli bacteria
b. If disabled, 30% of proteins fail to fold
2. More than17 kinds of proteins act as molecular chaperones
a. Include heat shock proteins
b. High temperature causes protein to unfold, heat shock Chaperonin help
refold
A. Sometimes amino acid sequence is correct but proteins fail to fold
B. In cystic fibrosis, a membrane transport protein (ions) fails to fold
C. May cause Alzheimer’s with protein clumping in brain tissues
A. Denaturation
1. Protein shape is altered with changes in pH, temperature,
ion concentration
2. Proteins become biologically inactive
3. Enzymes function only within a narrow environmental
range
B. Small proteins may return to natural shape when normal
environment is reestablished (renaturation)
1. Large proteins rarely refold naturally
2. Denaturation is different from dissociation
a. Subunits may dissociate without denaturing folded proteins
b. Can readily reassume subunit quaternary structure
Destruction of Conformation
= Loss of Function

Some simple proteins

can spontaneously
renature
“A protein’s
specific
conformation
determines
how it works.
In almost
every case,
the function
of a protein
depends on
its ability to
recognize
and bind to
some other
molecule.”