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3D Structure of Proteins - Coggle Diagram

- - - - strong disulfide (covalent) bonds are uncommon
      - weak (noncovalent) interactions and forces are numerous
        
        hydrogen bonds
        
        hydrophobic effect
        
        ionic interactions
  - - - decreases when nonpolar groups cluster together
      - decrease causes a favorable increase in net entropy
  - - - strength increases in an environment of lower dielectric constant
        
        dielectric constant of polar aqueous solvent is about 80
        
        dielectric constant of nonpolar protein interior is about 4
- - - - small proteins usually have only one domain
      - may appear as distinct or be difficult to discern
  - - - about 4,000 different protein families in the PDB
      - strong evolutionary relationship within a family
  - - - protomer = repeating structural unit
  - - - weak interactions and covalent bonds hold interacting segments in position
  - - - the structure of alpha-Keratin in hair
        
        a right handed alpha helix
        
        two strands of alpha keratin, oriented in parallel, wrap around each other to form a lefthanded supertwisted coiled coil
        
        hair contains many alpha-Keratin filaments
        
        rich in hydrophobic residues
        
        cross-links stabilized by disulfide bonds
      - The structure of collagen
        
        collagen is found in connective tissue
        
        the secondary structure is a left-handed, repeating tripeptide unit Gly - X - Y, where X is often Pro and Y is often 4-Hyp
        
        tertiary and quaternary structure is right handed twisting of three separate polypeptides
        
        covalent cross-links in collagen fibrils
        
        cross-linked by covalent bonds involving Lys, HyLys (5-hydroxylysine), or His, creating uncommon amino acid residues
        
        scurvy, vitamin C, and collagen formation
        
        scurvy is caused by a lack of vitamin C and characterized by general degeneration of connective tissue
        
        vitamin is required for the hydroxylation of proline and lysine in collagen
      - the structure of Fibroin
        
        main protein in silk
        
        predominantly beta conformation
        
        rich in Ala and Gly
        
        stabilized by hydrogen bonding and van der Waals interactions
  - - - the spatial coordinates of each atom
      - information on how the structure was determined
      - information on its accuracy
  - - - several structural representations of myoglobin's tertiary structure:
        
        binding pocket
        
        hydrophobic R chains
        
        alpha-helical regions
  - - - can be simple, such as in a beta-alpha-beta loop
      - can be elaborate, such as in a beta barrel
- - - - Hsp70 binds to hydrophobic regions
      - chaperonins are chambers required for the folding of proteins that do not fold spontaneously
  - - - misfolded beta amyloid promotes aggregation, forming an amyloid fibril - beta sheet aggregation
      - some diseases convert alpha helices to beta-sheets in the brain, known as prion proteins (PrP)
    - - Alzeimer disease is associated with extracellular amyloid deposition by neurons, involving the amyloid-beta peptide
      - Parkinson disease involves a misfolded form of alpha-synuclein aggregates into spherical filamentous masses called Lewy bodies
      - Huntington disease involves the intracellular aggregation of huntingtin, a protein with long polyglutamine repeat
      - cystic fibrosis is caused by defects in the membrane-bound protein cystic fibrosis transmembrane conductance regulator (CFTR)
        
        deletion of a Phe residue causes improper protein folding
- - - - the alpha helix, which is the simplest arrangement and contains the maximum number of hydrogen bonds
        
        backbone wound around an imaginary longitudinal axis
        
        R groups protrude out from the backbone
        
        each helical turn encompasses 3.6 residues
        
        intrahelical hydrogen bonds:
        
        occur between hydrogen atom attached to the electronegative nitrogen atom of residue n and the electronegative carbonyl oxygen atom of residue n + 4
        
        confers significant stability
        
        amino acid sequence affects stability of the alpha helix:
        
        amino acid residues have an intrinsic propensity to form an alpha helix
        
        interactions between R chains spaced 3-4 residues apart can stabilize or destabilize the alpha helix
        
        charge, size, and shape of R chains can destabilize
        
        formation of ion pairs and hydrophobic effect can stabilize
        
        Proline and Glycine occur infrequently in an alpha helix
        
        proline introduces a destabilizing kink in a helix
        
        nitrogen atom is part of a rigid ring
        
        rotation about N - C(alpha) bond not possible
        
        glycine has high conformational flexibility and takes up coiled structures
        
        Amino acid residues near the end of the alpha helix segment affect stability
        
        small electric dipoles in each peptide bond align through hydrogen bonds
        
        negatively charged amino acids often found near the NH3+ terminus
        
        positively charged amino acids often found near the COO- terminus
      - The beta conformation organizes polypeptide chains into sheets where the backbone extends into a zigzag
        
        forms:
        
        a beta sheet is several strands in beta conformation side by side
        
        a beta strand is a single protein segment
        
        beta turns connect two ends of two adjacent segments of an antiparallel beta sheet
        
        180 turn
        
        involves four residues
        
        hydrogen bond forms between first and fourth residue
        
        Gly (residue 2) and Pro (residue 3) often occur in beta turns
        
        adjacent polypeptide chains in a beta sheet can be antiparallel or parallel, and hydrogen bonds form between the backbone atoms of adjacent segments
        
        antiparallel sheets have opposite orientation and occur more frequently
        
        parallel sheets have the same orientation and are less common
- - - - limited to molecules that can be crystallized
      - information obtained depends on the degree of structural order in the sample
      - in x-ray crystallography, a pattern of diffracted s-rays is collected directly and an image is reconstructed by mathematical techniques
        
        steps:
        
        3D electron-density map using a Fourier transform
        
        Localized atomic nuclei
        
        completed protein structure
        
        X-ray diffraction patterns from protein crystals
        
        the physical environment in a crystal
        
        not identical to the physical environment in solution or in a living cell
        
        imposes a space and time average on the structure
        
        provides little information about molecular movement of protein
        
        crystal-derived structure usually represents a functional conformation
    - - carried out on molecules in solution
      - captures dynamics of protein structure
        
        conformational changes
        
        protein folding
        
        interactions with other molecules
      - determined by measuring nuclear spin angular momentum, a quantum mechanical property of atomic nuclei
        
        nuclear spin of 1H, 13C, 15N, 19F, and 31P gives rise to an NMR signal
        
        nuclear spin generates a magnetic dipole
      - NMR spectrum
        
        magnetic field causes magnetic dipoles to align in the field in one or two orientations:
        
        parallel -- low energy
        
        antiparallel -- high energy
        
        pulse of electromagnetic energy generates an NMR spectrum
      - 2D NMR techniques include:
        
        NOESY, which measures distance-dependent coupling of nuclear spins in nearby atoms through space
        
        TOCSY, which measures the coupling of nuclear spins in atoms connected by covalent bonds
    - - sample of the structure of interest is quick-frozen in vitreous (or noncrystalline) ice and kept frozen while being observed in 2D with the EM
        
        greatly reduces damage to the specimen