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    The Three-Dimensional Structure of Proteins

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    carlette11
    1) Proteins have four levels of structure: primary, secondary, tertiary, and quaternary. Secondary structure involves hydrogen bonding patterns like alpha helices and beta sheets. Tertiary structure describes the 3D folding of the polypeptide chain. Quaternary structure involves the assembly of multiple protein subunits. 2) Protein structures are stabilized by non-covalent interactions like hydrogen bonding, hydrophobic effects, and disulfide bridges. Denaturation disrupts these interactions and causes loss of biological activity. 3) Techniques like X-ray crystallography and NMR spectroscopy can determine high-resolution 3D protein structures. Hemoglobin and myoglobin were discussed as examples.

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    The Three-Dimensional Structure of Proteins

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    carlette11
    22 views21 pages
    1) Proteins have four levels of structure: primary, secondary, tertiary, and quaternary. Secondary structure involves hydrogen bonding patterns like alpha helices and beta sheets. Tertiary structure describes the 3D folding of the polypeptide chain. Quaternary structure involves the assembly of multiple protein subunits. 2) Protein structures are stabilized by non-covalent interactions like hydrogen bonding, hydrophobic effects, and disulfide bridges. Denaturation disrupts these interactions and causes loss of biological activity. 3) Techniques like X-ray crystallography and NMR spectroscopy can determine high-resolution 3D protein structures. Hemoglobin and myoglobin were discussed as examples.

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    1) Proteins have four levels of structure: primary, secondary, tertiary, and quaternary. Secondary structure involves hydrogen bonding patterns like alpha helices and beta sheets. Tertiary structure describes the 3D folding of the polypeptide chain. Quaternary structure involves the assembly of multiple protein subunits. 2) Protein structures are stabilized by non-covalent interactions like hydrogen bonding, hydrophobic effects, and disulfide bridges. Denaturation disrupts these interactions and causes loss of biological activity. 3) Techniques like X-ray crystallography and NMR spectroscopy can determine high-resolution 3D protein structures. Hemoglobin and myoglobin were discussed as examples.

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    22 views21 pages

    The Three-Dimensional Structure of Proteins

    Uploaded by

    carlette11
    1) Proteins have four levels of structure: primary, secondary, tertiary, and quaternary. Secondary structure involves hydrogen bonding patterns like alpha helices and beta sheets. Tertiary structure describes the 3D folding of the polypeptide chain. Quaternary structure involves the assembly of multiple protein subunits. 2) Protein structures are stabilized by non-covalent interactions like hydrogen bonding, hydrophobic effects, and disulfide bridges. Denaturation disrupts these interactions and causes loss of biological activity. 3) Techniques like X-ray crystallography and NMR spectroscopy can determine high-resolution 3D protein structures. Hemoglobin and myoglobin were discussed as examples.

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    of 21

    Mary K.

    Campbell
    Shawn O. Farrell
    international.cengage.com/

    The Three-Dimensional Structure of


    Proteins

    Paul D. Adams University of Arkansas

    Protein Structure
    Many conformations are possible for proteins:
    Due to flexibility of amino acids linked by peptide
    bonds

    At least one major conformations has biological


    activity, and hence is considered the proteins native
    conformation

    Levels of Protein Structure


    1structure: the sequence of amino acids in a
    polypeptide chain, read from the N-terminal end to
    the C-terminal end
    2structure: the ordered 3-dimensional
    arrangements (conformations) in localized regions of
    a polypeptide chain; refers only to interactions of the
    peptide backbone
    e. g., -helix and -pleated sheet

    3 structure: 3-D arrangement of all atoms


    4 structure: arrangement of monomer subunits with
    respect to each other

    1 Structure
    The 1 sequence of proteins determines its 3-D
    conformation
    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 hydrogenbonded arrangement of
    backbone of the protein
    Two bonds have free
    rotation:
    1) Bond between -carbon
    and amino nitrogen in
    residue
    2) Bond between the carbon and carboxyl
    carbon of residue

    -Helix

    Coil of the helix is clockwise or right-handed


    There are 3.6 amino acids per turn
    Repeat distance is 5.4
    Each peptide bond is s-trans and planar
    C=O of each peptide bond is hydrogen bonded to the
    N-H of the fourth amino acid away
    C=O----H-N hydrogen bonds are parallel to helical
    axis
    All R groups point outward from helix

    -Helix (Contd)

    -Helix (Contd)
    Several factors can disrupt an -helix
    proline 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 bonding
    strong electrostatic repulsion caused by the proximity
    of several side chains of like charge, e.g., Lys and Arg
    or Glu and Asp
    steric crowding caused by the proximity of bulky side
    chains, e.g., Val, Ile, Thr

    -Pleated Sheet
    Polypeptide chains lie adjacent to one another; may
    be parallel or antiparallel
    R groups alternate, first above and then below plane
    Each peptide bond is s-trans and planar
    C=O and N-H groups of each peptide bond are
    perpendicular to axis of the sheet
    C=O---H-N hydrogen bonds are between adjacent
    sheets and perpendicular to the direction of the sheet

    -Pleated Sheet (Contd)

    -Pleated Sheet (Contd)


    -bulge- a common non-repetitive irregular 2 motif in
    anti-parallel structure

    Structures of Reverse Turns


    Glycine found in reverse turns
    Spatial (steric) reasons

    Polypeptide changes direction


    Proline also encountered in reverse turns. Why?

    -Helices and -Sheets


    Supersecondary structures: the combination of and -sections, as for example
    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
    itself
    -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 tropocollagen; 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 -helix
    The three strands are held together by hydrogen
    bonding involving hydroxyproline and hydroxylysine
    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
    keratin of hair and wool
    collagen 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 water and salt 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 buried inside
    nearly all have substantial sections of -helix and sheet

    Comparison of Shapes of Fibrous and


    Globular Proteins

    3 Structure

    The 3-dimensional arrangement of atoms in the


    molecule.
    In fibrous protein, backbone of protein does not fall
    back on itself, it is important aspect of 3 not specified
    by 2 structure.
    In globular 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 side chains also plays a role.

    Forces in 3 Structure
    Noncovalent interactions, including
    hydrogen bonding between polar side chains, e.g., Ser
    and Thr
    hydrophobic interaction between nonpolar side chains,
    e.g., Val and Ile
    electrostatic attraction between side chains of opposite
    charge, e.g., Lys and Glu
    electrostatic repulsion between side chains of like
    charge, e.g., Lys and Arg, Glu and Asp

    Covalent interactions: Disulfide (-S-S-) bonds


    between side chains of cysteines

    10

    Forces That Stabilize Protein Structure

    3and 4Structure
    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 2and 3structure

    Quaternary (4) structure: the association of


    polypeptide chains into aggregations
    Proteins are divided into two large classes based on
    their three-dimensional structure
    fibrous proteins
    globular proteins

    11

    Determination of 3Structure
    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 diffraction
    patterns
    information on molecular coordinates is extracted by a
    mathematical analysis called a Fourier series

    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

    12

    Myoglobin

    A single polypeptide chain of 153 amino acids


    A single heme group in a hydrophobic pocket
    8 regions of -helix; no regions of -sheet
    Most polar side chains are on the surface
    Nonpolar side chains are folded to the interior
    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

    13

    Oxygen Binding Site of Myoglobin

    Denaturation
    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

    14

    Denaturation of a Protein

    Denaturation and Refolding in


    Ribonuclease
    Several ways to denature
    proteins
    Heat
    pH
    Detergents
    Urea
    Guanadine hydrochloride

    15

    Quaternary Structure
    Quaternary (4) structure: the association of
    polypepetide monomers into multisubunit proteins
    dimers
    trimers
    tetramers

    Noncovalent interactions
    electrostatics, hydrogen bonds, hydrophobic

    Oxygen Binding of Hemoglobin (Hb)


    A tetramer of two -chains (141 amino acids each)
    and two -chains (153 amino acids each); 22
    Each chain has 1 heme group; hemoglobin can bind
    up to 4 molecules of O2
    Binding of O2 exhibited by positive cooperativity;
    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-bisphosphoglycerate (BPG)
    affect the ability of Hb to bind and transport oxygen

    16

    Structure of Hemoglobin

    Conformation Changes That Accompany Hb Function

    Structural changes occur during binding of small


    molecules

    Characteristic of allosteric behavior


    Hb exhibits different 4 structure in the bound and
    unbound oxygenated forms
    Other ligands are involved in cooperative effect of Hb
    can affect proteins affinity for O2 by altering structure

    17

    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

    18

    Predicting Protein Structure


    Biochemistry and computing
    together gave rise to the field
    of bioinformatics

    Predicting protein
    architecture is a search of
    databases of known structures
    for sequence homology
    Homology- Refers to
    similarity of two or more
    sequences

    Predicted vs. Actual Protein Structures

    19

    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 environment
    Hydrophobic interactions are spontaneous

    Hydrophobic and Hydrophilic Interactions in Proteins

    20

    Protein Folding Chaperones


    In the protein-dense environment of a cell, proteins
    may begin to fold incorrectly or may associate with
    other proteins before folding is completed

    Special proteins called chaperones aid in the correct


    and timely folding of many proteins
    hsp70 were the first chaperone proteins discovered
    Chaperones exist in organisms from prokaryotes to
    humans

    21

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