Protein Structure and function

• Alpha helix

  1. H and C=O groups are hydrogen bonded to one another, 3.6 amino acids per turn, C=O group of amino acid n is hydrogen bonded to the N-H group of amino acid n+4
• Beta sheet

  Non-continuous regions of the polypeptide chain, beta strands line up and form hydrogen bonds between the C=O groups of one strand and the N-H groups of another, If the strands all run in the same direction (N to C) then the beta sheet is described as PARALLEL. If the strands run in opposite directions then it is said to be ANTI-PARALLEL
• Role of loop regions

  Joining together elements of secondary structure
• Proteins are always synthesised using the same set of 20 amino acids
• Post-translational modifications

  Alterations to some amino acids produce "rare" amino acids like hydroxyproline, hydroxylysine, Sugars/carbohydrates/glycans can be added (glycosylation - glycoproteins), Lipids can also be added (lipoproteins), These modifications can contribute to secondary structure
• For most proteins, the final three-dimensional structure is produced by the association of the secondary structures into compact domains, called TERTIARY STRUCTURE
• Primary structure:

  sequence of amino acids from the N-terminal to C-terminal
• Secondary structure:

  Folding of primary structure into particular structures

  alpha or beta folding
• protein folding:

  main driving force is energtically stable structure

  Water soluble proteins its a hydrophobic side chains into interiors (hydrophobic core)

  hydrogen bonds between C=O and N-H
• alpha helix:

  formed from stretches of 5-40 amino acids

  Main chain is the hydrogen bonds between the N-H and C=O

  Side chain project out from the edge of the helix

  Each residue is plotted 100 degrees around a circle/ spiral
• Parallel beta sheet:

  • Have evenly spaced hydrogen bonds in the sheet
  • beta are in an almost fully extended conformation
  • beta strands run in the same direction
• Anti-parallel beta sheet:

  • narrowly space H bonds pairs separated by a larger gap
  • beta strands are almost fully extended conformation
  • run in opposite directions
• Pleated sheet structure:

  The alpha C lies succesively above and below the plane of the sheet
• Loop region:

  Areas that link secondary structure

  • vary in length
  • long loops are called random coils and are highly flexible parts of protein
  • Short loops regions which connect anti-parallel beta strands are called hairpin loops or beta turns
• Common loop groups:

  • proline: its locked ring structure introduces a kink inot the polypeptide chain
  • Glycine: small side chain enables it to form turns when other amino acids cant
• What is a beta-alpha-beta motive?


  composed of two beta strands joined by an alpha helix through connecting loops
• Anti-parallel beta strands are usually connected by hairpin loop
• Parallel beat strands are usually connected by an alpha helix
• Tertiary structure

  Correctly folded compact domains formed by the association of secondary structures
• Tertiary structure

  • Non-covalent bonds are important: ionic bonds, hydrogen bonds, van der Waals forces
• Disulphide bridges

  Covalent bonds formed between the side chains of two cysteine residues, making proteins more resistant to degradation and denaturation
• Diagrammatic representation of tertiary structure

  • Polypeptide backbone shown as thick line or ribbon, α-helices shown as spirals or cylinders, β-strands shown as arrows
• Proteins with tertiary structure

  • Triosephosphate isomerase
  • Myoglobin
  • Cytochrome b
  • Thioredoxin
• Quaternary structure

  Proteins formed from more than one polypeptide chain, with the chains (subunits) associated into a multimeric complex held together by non-covalent bonds
• Proteins with quaternary structure


  • Haemoglobin
  • Antibodies
• Primary structure

  • Sequence of amino acids forming the polypeptide chain and position of disulphide cross-links
• Secondary structure

  • Regular local structures like α-helices and β-sheets
• Tertiary structure

  • Packing of secondary structural elements into compact globular domains
• Globular proteins

  Protein chains arranged in compact domains, usually active cellular components
• Fibrous proteins

  Protein chains arranged into fibres, have a structural role
• Fibrous protein groups

  • Coiled-coil (e.g. keratin, myosin)
  • β-sheets (e.g. amyloid, silk)
  • Triple helix (collagen)
• α-Keratin

  • Two α-helices twist around each other, forming a coiled-coil structure
  • primary structure: a-b-c-d-e-f-g, residues a and d are hydrophobic and lie on same side of alpha helix, the rest can be any amino acid
• Silk fibroin

  • Long stretches of antiparallel β-sheets formed from a six amino acid repeat
  • one side has glycine side chains (H) and the other side has the side chains of serine and alanine (CH2OH) (CH3)
• Collagen

  • Forms a 'loose' helix with three residues per turn, due to proline and hydroxyproline residues
  • Nearly one-third glycine, 15-30% proline or hydroxyproline
  • Three polypeptide chains form a triple helix
• How does alpha keratin form microfibrils

  1. the coiled-coil dimer lines up with another to form a staggered antiparallel tetramers
  2. The tetramers are the building blocks of protofilaments
  3. The protofilaments form protofibrils
  4. Protofibrils form microfibrils
• Why is silk strong?

  As any stretching would require the breaking of covalent bonds
• Why is silk flexible?

  Beta sheets are interacting via weak van der waals bonds
• Collagen triple helix:

  every 3rd amino acid passes through the centre of the triple helix which is so crowed that only glycine can fit

  Pro and hyp confer rigidity

  Polypeptide chains form inter-chain hydrogen bonds

  The triple-helical trimers can often associate to form large, strong fibres