Chapter Four The Three-Dimensional Structure of Proteins - PowerPoint PPT Presentation

View by Category
About This Presentation

Chapter Four The Three-Dimensional Structure of Proteins


The Three-Dimensional Structure of Proteins Conformation Changes That Accompany Hb Function Structural changes occur during binding of small molecules ... – PowerPoint PPT presentation

Number of Views:373
Avg rating:3.0/5.0
Slides: 41
Provided by: BillB203


Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Chapter Four The Three-Dimensional Structure of Proteins

Chapter FourThe Three-Dimensional Structure of
Protein Structure
  • Many _________________ are possible for proteins
  • Due to flexibility of amino acids linked by
    peptide bonds
  • At least one major _________________ has
    biological activity, and hence is considered the
    proteins _______________ _________________

Levels of Protein Structure
  • ___ structure the ________________ of amino
    acids in a polypeptide chain, read from the
    N-terminal end to the C-terminal end
  • ___ structure the ______________ ______________
    arrangements (conformations) in localized regions
    of a polypeptide chain refers only to
    interactions of the peptide backbone e. g.,
    ?-helix and ?-pleated sheet
  • ___ structure 3-D arrangement of all atoms
  • ___ structure arrangement of monomer subunits
    with respect to each other

1 Structure
  • The 1 sequence of proteins determines its 3-D
  • Changes in just one amino acid in sequence can
    alter biological function, e.g. hemoglobin
    associated with sickle-cell anemia
  • Determination of 1 sequence is routine
    biochemistry lab work (See Ch. 5).

2 Structure
  • 2 of proteins is hydrogen-bonded arrangement
    of _________________ of the protein
  • Two bonds have _____________ ____________
  • Bond between _________________ and
    _________________ in residue
  • Bond between the _________________ and
    _________________ of residue
  • See Figure 4.1

  • Coil of the helix is ___________ or _____________
  • There are ______ amino acids per turn
  • Repeat distance is _____ Å
  • Each peptide bond is _________ and ________
  • CO of each peptide bond is _________________
    _________ to the N-H of the fourth amino acid
  • CO----H-N hydrogen bonds are ________________
    helical axis
  • All R groups point _________________ from helix

?-Helix (Contd)
?-Helix (Contd)
  • Several factors can _______________ an ?-helix
  • _______ creates a bend because of (1) the
    restricted rotation due to its cyclic structure
    and (2) its ?-amino group has no N-H for hydrogen
  • strong _________________ _________________ caused
    by the proximity of several side chains of like
    charge, e.g., Lys and Arg or Glu and Asp
  • _________________ _________________ caused by the
    proximity of bulky side chains, e.g., Val, Ile,

?-Pleated Sheet
  • Polypeptide chains lie adjacent to one another
    may be _________________ or _________________
  • R groups ________, first above, then below
  • Each peptide bond is ________ and ________
  • CO and N-H groups of each peptide bond are
    ____________ to axis of the sheet
  • CO---H-N hydrogen bonds are between adjacent
    sheets and ____________ to the direction of the

?-Pleated Sheet (Contd)
?-Pleated Sheet (Contd)
  • ?-bulge- a common nonrepetive irregular 2 motif
    in ____________ structure

Structures of Reverse Turns
  • ____________ found in reverse turns
  • Spatial (steric) reasons
  • Polypeptide changes direction
  • ____________ also encountered in reverse turns.

?-Helices and ?-Sheets
  • __________________ structures the combination of
    ?- and ?-sections, as for example
  • ??b unit two parallel strands of ?-sheet
    connected by a stretch of ?-helix
  • ?? unit two antiparallel ?-helices
  • ?-meander an antiparallel sheet formed by a
    series of tight reverse turns connecting
    stretches of a polypeptide chain
  • Greek key a repetitive supersecondary structure
    formed when an antiparallel sheet doubles back on
  • ?-barrel created when ?-sheets are extensive
    enough to fold back on themselves

Schematic Diagrams of Supersecondary Structures
Collagen Triple Helix
  • Consists of three polypeptide chains wrapped
    around each other in a ropelike twist to form a
    triple helix called __________________ MW
    approx. 300,000
  • 30 of amino acids in each chain are Pro and Hyp
    (hydroxyproline) hydroxylysine also occurs
  • Every third position is Gly and repeating
    sequences are X-Pro-Gly and X-Hyp-Gly
  • Each polypeptide chain is a helix but not an
  • The three strands are held together by hydrogen
    bonding involving hydroxyproline and
  • With age, collagen helices become cross linked by
    covalent bonds formed between Lys and His residues

Fibrous Proteins
  • Fibrous proteins contain polypeptide chains
    organized approximately parallel along a single
    axis. They
  • consist of long fibers or large sheets
  • tend to be mechanically strong
  • are insoluble in water and dilute salt solutions
  • play important structural roles in nature
  • Examples are
  • ____________ of hair and wool
  • ____________ of connective tissue of animals
    including cartilage, bones, teeth, skin, and
    blood vessels

Globular Proteins
  • Globular proteins proteins which are folded to a
    more or less spherical shape
  • they tend to be soluble in ____________ and
    ____________ solutions
  • most of their polar side chains are on the
    outside and interact with the aqueous environment
    by hydrogen bonding and ion-dipole interactions
  • most of their nonpolar side chains are ______
  • nearly all have substantial sections of
    _____________ and ____________

Comparison of Shapes of Fibrous and Globular
3 Structure
  • The ____________ arrangement of atoms in the
  • In ____________ protein, backbone of protein does
    not fall back on itself, it is important aspect
    of 3 not specified by 2 structure.
  • In ____________ protein, more information needed.
    3k structure allows for the determination of the
    way helical and pleated-sheet sections fold back
    on each other.
  • Interactions between ______ ______ also plays a

Forces in 3 Structure
  • _________ interactions, including
  • _________ _________ between polar side chains,
    e.g., Ser and Thr
  • _________ interaction between nonpolar side
    chains, e.g., Val and Ile
  • _________ _________ between side chains of
    opposite charge, e.g., Lys and Glu
  • _________ _________ between side chains of like
    charge, e.g., Lys and Arg, Glu and Asp
  • _________ interactions Disulfide (-S-S-) bonds
    between side chains of _________

Forces That Stabilize Protein Structure
3 and 4 Structure
  • Tertiary (3) structure the arrangement in space
    of all atoms in a polypeptide chain
  • it is not always possible to draw a clear
    distinction between _________ and _________
  • Quaternary (4) structure the association of
    polypeptide chains into _________
  • Proteins are divided into two large classes based
    on their three-dimensional structure
  • _________ proteins
  • _________ proteins

Determination of 3 Structure
  • X-ray crystallography
  • uses a perfect crystal that is, one in which all
    individual protein molecules have the same 3D
    structure and orientation
  • exposure to a beam of x-rays gives a series of
    diffraction patterns
  • information on molecular coordinates is extracted
    by a mathematical analysis called a Fourier
  • 2-D Nuclear magnetic resonance
  • can be done on protein samples in aqueous solution

X-Ray and NMR Data
High resolution method to determine 3 structure
of proteins (from crystal) Diffraction pattern
produced by electrons scattering X-rays Series of
patterns taken at different angles gives
structural information
Determines solution structure Structural info.
Gained from determining distances between nuclei
that aid in structure determination
  • A single polypeptide chain of ____ amino acids
  • A single ______ group in a _____________ pocket
  • 8 regions of ?-helix no regions of ?-sheet
  • Most _______ side chains are on the __________
  • ________ side chains are folded to the __________
  • Two His side chains are in the interior, involved
    with interaction with the heme group
  • Fe(II) of heme has 6 coordinates sites 4
    interact with N atoms of heme, 1 with N of a His
    side chain, and 1 with either an O2 molecule or
    an N of the second His side chain

The Structure of Myoglobin
Oxygen Binding Site of Myoglobin
  • Denaturation the loss of the structural order
    (2, 3, 4, or a combination of these) that
    gives a protein its biological activity that is,
    the loss of biological activity
  • Denaturation can be brought about by
  • heat
  • large changes in pH, which alter charges on side
    chains, e.g., -COO- to -COOH or -NH? to -NH?
  • detergents such as sodium dodecyl sulfate (SDS)
    which disrupt hydrophobic interactions
  • urea or guanidine, which disrupt hydrogen bonding
  • mercaptoethanol, which reduces disulfide bonds

Denaturation of a Protein
Denaturation and Refolding in Ribonuclease
Several ways to denature proteins Heat
pH  Detergents Urea Guanadine hydrochloride
Quaternary Structure
  • Quaternary (4) structure the association of
    polypepetide ________ into _____________ proteins
  • dimers
  • trimers
  • tetramers
  • Noncovalent interactions
  • electrostatics, hydrogen bonds, hydrophobic

Oxygen Binding of Hemoglobin (Hb)
  • A _________ of two ?-chains (141 amino acids
    each) and two ?-chains (153 amino acids each)
  • Each chain has 1 heme group hemoglobin can bind
    up to 4 molecules of O2
  • Binding of O2 exhibited by _________ ___________
    when one O2 is bound, it becomes easier for the
    next O2 to bind
  • The function of hemoglobin is to transport oxygen
  • The structure of oxygenated Hb is different from
    that of unoxygenated Hb
  • H, CO2, Cl-, and 2,3-_______________ (BPG)
    affect the ability of Hb to _________ ________

Structure of Hemoglobin
Conformation Changes That Accompany Hb Function
  • Structural changes occur during binding of
    small molecules
  • Characteristic of __________________ behavior
  • Hb exhibits different 4 structure in the bound
    and unbound oxygenated forms
  • Other _________ are involved in cooperative
    effect of Hb can affect proteins affinity for O2
    by altering structure

Oxy- and Deoxyhemoglobin
Protein Folding Dynamics
  •  Can 3 structure of protein be predicted? Yes,
    within limitations
  • The integration of biochemistry and computing
    has led to bioinformatics
  • Protein structure prediction is one of the
    principal application of bioinformatics
  • First step to predict protein structure is to
    search for sequence homology

Predicting Protein Structure
Hydrophobic Interactions
  • Hydrophobic interactions are major factors in
    protein folding
  • Folds so that nonpolar hydrophobic side chains
    tend to be on inside away from water, and polar
    side chains on outside accessible to aqueous
  • Hydrophobic interactions are __________________

Hydrophobic and Hydrophilic Interactions in
Protein Folding Chaperones
  • In the protein-dense environment of a cell,
    proteins may begin to fold _________ or may
    associate with other proteins before folding is
  • Special proteins called _________ aid in the
    correct and timely _________ of many proteins
  • hsp70 were the first chaperone proteins
  • Chaperones exist in organisms from prokaryotes to