Transcript Powerpoint slides

PROTEIN STRUCTURE (Donaldson, March 10,2003)
What are we trying to learn about genes and their proteins:
Predict function for unknown protein by comparison to known
proteins.
Determine the relationship of proteins to each other evolutionary history.
Alignment of amino acid sequences suggests common
functions.
Three dimensional structure of an unknown protein may give
clues to function. Compare with 3D structures of known
proteins.
Evolutionary tree showing
how the globin protein
family arose, starting from
the most primitive oxygenbinding proteins,
leghemoglobins, in plants.
Molecular Cell Biology. 4th ed. Lodish, :
W H Freeman & Co; c2000.
Figure 5.23 The quaternary structure of proteins
Evolutionary of like globin
chains that carry oxygen in
the blood of animals. A
relatively recent gene
duplication of the -chain
gene produced  G and  A,
which are fetal -like chains
of identical function. The
location of the globin genes in
the human genome is shown
at the top.
Molecular Biology of the Cell. 3rd ed.
Alberts, Garland Publishing; c1994
A comparison of the structure
of one-chain and four-chain
globins. The four-chain globin
shown is hemoglobin, which is
a complex of two - and two globin chains. The one-chain
globin in some primitive
vertebrates forms a dimer that
dissociates when it binds
oxygen, representing an
intermediate in the evolution of
the four-chain globin.
Molecular Biology of the Cell. 3rd ed. Alberts,
Garland Publishing; c1994
Protein Structures
The features and forces of proteins structure
Primary sequence of amino acids
Secondary interactions form coils and sheets
Tertiary interactions cause coils and sheets to fold upon
each other.
Quaternary interactions between separate protein
molecules result in multi-subunit structures.
Techniques used to determine protein structure.
Hemoglobin will be the main example
What are the forces between amino acid residues in a protein?
Ionic interactions between oppositely charged residues
can pull them together.
Hydrogen Bonds - Hydrogens are partially positively
charged, are attracted to partially negative oxygens. (weaker)
van Der Waals - hydrophobic residues become attractive
to each other when forced together by exclusion from the aqueous
surroundings. (weakest)
Figure 5.22 Examples of interactions contributing to the tertiary structure of a protein
Figure 5.24 Review: the four levels of protein structure
Figure 5.26 A chaperonin in action
Protein structures are determined by two techniques
X-ray diffraction of pure protein crystal
Nuclear Magnetic Resonance of smaller protein molecule
Usually in solution
Figure 5.27 X-ray crystallography
1864 Hoppe-Seyler crystallized, and named, the
protein hemoglobin.
1895 Ršntgen observed that a new form of
penetrating radiation, which he named xrays, was produced when cathode rays
(electrons) hit a metal target.
1935 Patterson developed an analytical method
for determining interatomic spacings from xray data.
1941 Astbury obtained the first x-ray diffraction
pattern of DNA.
1912 W.L. Bragg proposed a simple relationship
between an x-ray diffraction pattern and the
arrangement of atoms in a crystal that
produced the pattern.
1951 Pauling and Corey proposed the structure of
a helical conformation of a chain of L-amino
acids - the a-helix - and the structure of the
b-sheet, both of which were later found in
many proteins.
1926 Summer obtained crystals of the enzyme
urease from extracts of jack beans and
demonstrated that proteins possess catalytic
activity.
1953 Watson and Crick proposed the double-helix
model of DNA, based on x-ray diffraction
patterns obtained by Franklin and Wilkins.
1931 Pauling published his first essays on "The
Nature of the Chemical Bond," detailing the
rules of covalent bonding.
1954 Perutz and colleagues developed heavy-atom
methods to solve the phase problem in
protein crystallography.
1934 Bernal and Crowfoot presented the first
detailed x-ray diffraction patterns of a
protein obtained from crystals of the enzyme
pepsin.
1960 Kendrew described the first detailed
structure of a protein (sperm whale
myoglobin) to a resolution of 0.2 nm, and
Perutz proposed a lower-resolution structure
of the larger protein hemoglobin.
Figure 6.14 The induced fit between an enzyme and its substrate