Structure of proteins 1

• What are the functions of proteins?


  • Provide structure
  • Collagen in bone, skin and tendons
  • Transport molecules
  • haemoglobin carries oxygen
  • LDL and LDL receptor - transport cholesterol molecules and co-ordinate their uptake into cells
  • Defence
  • antibodies - defence against infection
  • Biological catalysts
  • enzymes - regulation of all biological systems
  • Regulation of genes
  • Lac repressor - helps to control gene expression
• Describe some aspects of collagen


  • most abundant protein in mammals
  • main component of connective tissue
  • found in skin, tendons, organs and bone
• What is the structure and function of haemoglobin?


  • Selective delivery of O2 to metabolic tissues
  • 4 protein subunits per molecule
  • Each subunit contains a Haem group that can bind one oxygen molecule
  • Haem is an example of a prosthetic group
  • Erythrocytes - red blood cells
  • Haem is a porphyrin ring - contains iron
• What is a prosthetic group in proteins?


  A non-peptide compound that mostly attaches to a protein group to assist them in different ways

  • can be organic (contain a carbon) or non-organic (metals)
• Describe the mechanisms of cholesterol transport


  • LDL (low density lipoprotein) is composed of a phospholipid shell and a single molecule of apoliprotein B
  • Used to transport cholesterol between cells via the circulatory system
  • The uptake of LDL particles is mediated by an LDL receptor that binds LDL and facilitates internalisation
• What is familial hypercholesterolemia


  When patients have a mutation in the LDL receptor gene.
• Describe antibody structure


  • two identical heavy chains and two identical light chains covalently linked by disulphide bonds
  • The antigen recognition site is highly specific and tightly binds the complementary antigen allowing recognition of foreign proteins by the immune system
  • Examples of gylcoproteins - contain sugars
  • Y - shaped
• Explain the mechanisms of the enzyme lysozyme


  • catalyses the cutting of the polysaccharide chains
  • Lysozyme binds to the polysaccharide chain, catalyzes the cleavage of a specific covalent bond and releases the cleaved products
  • Lysozyme remains unchanged at the end of the process
• Explain the mechanisms of the lac repressor in gene expression 


  • Controls the production (expression) of proteins metabolising lactose in bacteria
  • The repressor binds to DNA and prevents expression of the gene in the absence of lactose
• In proteins, what does the function depend on?


  • the property of specific binding
  • binding depends on conformation - if you change the conformation, you change the activity
• What is a linear polymer?


  Amino acids joined by peptide bonds
• What is the hierarchy of protein structure?


  1. primary - the sequence of amino acids linked together to form a poly peptide chain
  2. secondary - the regular, local structure of the protein backbone, stabilised by intamolecular and sometimes intermolecular hydrogen bonding of amide groups
  3. tertiary - The overall 3d arrangement of the polypeptide chain
  4. quaternary - The association of several protein chains or subunits into a closely packed arrangement
• What is the general structure of amino acids?


  Amino acids have a central carbon atom (alpha carbon) bonded to an amino group, a carboxyl group, a hydrogen atom, and a side chain - the side chain in specific to every amino acid

  • the chemical properties of each R group defines the structure and function of the protein.
• What are the different classification of amino acids?


  • hydrophillic amino acids
  • basic amino acids - can be positively charged and often are
  • Lysine - has an NH3+ group
  • Arginine - has an NH2+ group
  • HIstidine - has a nitrogen within an imidazole ring
  • acidic amino acids - have COO - groups, can become COOH
  • aspartate
  • glutatmate
  • Polar amino acids with uncharged R groups
  • Serine - have OH group
  • Threenine have OH group - slightly polar
  • Glutamine - Have amine group
  • Asparagine - have amine group
• What are the different classification of amino acids?


  • Hydrophobic amino acids - tend to be quite hydrocarbon rich, oily property, often buried within a protein structure
  • Alanine - hydrocarbon chain
  • Valine - hydrocarbon chain
  • Isoleucine - hydrocarbon chain
  • Leucine - hydrocarbon chain
  • Methionine - hydrocarbon chain
  • Phenylalanine - Aromatic amino acid - benzene ring
  • Tyrosine - aromatic amino acid - benzene ring
  • Tryptophan - aromatic amino acid - benzene ring
• What are the special amino acids and why are they different from the others?


  • Cysteine - contains - sulphur/thiol group - this protein forms disulphide bonds - helps to link different protein chains together
  • Glycine - smallest amino acid, R group is single H, can fit in very tight space
  • Proline - R group bends round to form a bond with the amino group, ring like structure can create a kink in the protein chain - kink breaks the secondary structure - makes it difficult to form
• Draw the structure of glycine and give its 3 letter code


  Glycine - Gly or G

  
• Draw the structure of proline and give the 3 letter code


  Proline - Pro or P

  
• Draw the structure of cysteine and give its 3 letter code


  Cysteine - Cys or C

  
• Draw the structure of histadine and give the 3 letter code 


  Histadine - His or H

  
• Draw the structure of aspartate and give the 3 letter code

  Aspartate - Asp or D

  
• What is an acid?


  Any moelcule that tends to release a hydrogen ion
• What is a base?


  A molecule that readily combines with a hydrogen ion
• What is the Pka?


  The pKa of any acid is equal to the pH at which half the molecules are disassociated
• What is the biological significance of pKa?


  • The overall charge of an amino acid - and therefore protein - varies with pH
  • pKa is the pH at which dissociation is 50% complete
  • Local environment can influence pKa
  • Dissociation largely occurs over 2pH unites centred on the pKa
  • Small changes in pH can cause significant changes in the charges carried
• Describe the process of receptor mediated endocytosis


  example - uptake of low density lipoprotein

  • reduction in pH in the endosome causes a change in conformation of the LDL receptor due to the presence of histidine residues within the protein (pK 6.5)
  • LDL can no longer bind and is released in the lysosome
  • Patients with familial hypercholesterolemia frequently have mutations in the histidine residues of the LDL receptor
• What is a polypeptide?


  A polymer of amino acids joined by peptide bonds

  • At one end there is an amino terminus (N-terminus) at the other side there is a carboxyl terminus (c-terminus)
  • On the horizontal sides, you have your R groups that often alternate between one side and the other - each side can tend towards more hydrophobic or hydrophillic - lend itself where a protein folds and the hydrophobics tend towards the inside and hydrophillics tend towards the outside
• Describe a peptide bond


  • covalent bond formed when the carbon from the carboxylate group shares electrons with the nitrogen atom from the amino group of a second amino acid
  • a molecule of water is lost so this is called a condensation reaction
• What are the constraints on a peptide bond?


  • Peptide bond does not permit rotation
  • Rotation can occur on the alpha carbon
  • The conformation of the folded polypeptide chain is determined by one pair of angles for each amino acid residue
  • Bulky R groups are positioned on either side of the backbone
  • This limits the number of 3-dimensional conformations possible for a polypeptide
• Describe the secondary structure


  • initial folding pattern (periodic repeats) of the linear polypeptide
  • 3 main types;
  • alpha helix
  • beta sheet
  • bend/loop
  • secondary structures are stabilised by hydrogen bonds
• Describe the alpha helix of secondary structures


  • right handed - each turn has 3.6 amino acid residues
  • the helix is stabilised by hydrogen bonds between amino and carboxyl groups of every 4th amino acid
• Describe the beta sheet of secondary structure

  • extended stretched of 5 or more amino acids are called beta strands
  • beta strands organised next to each other make beat sheets
  • Hydrogen bonding pattern varies depending on type of sheet
• What are parallel beta sheets?


  If the adjacent strands are oriented in the same direction (N-end to C-end)
• What are anti parallel beta sheets?


  If adjacent strands run opposite to each other then this is antiparallel
• Can you get mixed beta sheets?


  Yes, this is when there is a mix of parallel and anti parallel sheets
• Describe the secondary structure of bends/loop


  • polypeptide chains can fold upon themselves forming a bend or a loop
  • usually 4 amino acids are required to form the turn
  • Proline residues frequently found in bends/loops