Introduction to Protein Structure- Biomedicine in Relation to Dentistry 1

• What can misfolded proteins also cause?

  Formation of stable aggregations of proteins e.g. amyloid proteins forming plaques in Alzheimer's disease or prion protein polymerisation in Creutzfeldt-Jakob disease
• How is sickle cell disease caused?

  Glu--> Val (charged to hydrophobic), stabilising the polymerisation of Hb
• What does the amino acid sequence encode for other than the final structure?

  The pathway that leads to that structure
• Which amino acids are ionised at physiological pH?

  Carboxylic groups of Asp & Glu are ionised (COO-)

  Amino groups of Lys & Arg are ionised (NH3+)
• What are some examples of H bond donors and acceptors?

  H bond donors:

  O e.g. O-H (side chain of Ser, Thr, Tyr)

  N e.g. N-H (peptide bond, Trp, His, Arg) or NH3+ (Lys, Arg)

  H bond acceptors:

  O e.g. C=O carbonyl (peptide bond)

  Triple bonded N (Trp, His)
• What is the structure of the collagen triple helix?

  3 chains with H bonds between chains

  3 residues/turns

  Left-handed helix

  Every 3rd aa is Gly: Gly-X-Y-Gly-X-Y

  X= mainly proline, Y= mainly hydroxy-proline
• What are the 2 types of beta-sheet structures?

  (A)- antiparallel beta-sheet and (B)- parallel beta-sheet
• What is the structure of a beta-pleated sheet and how does it maintain this shape?

  Linear peptide chain with side chains in each strand alternately lying above & below the plane of the sheet. H bonding between peptide chains holds strands together in a beta-sheet
• Describe the structure of an alpha helix.

  Regular right-handed helix

  3.6 aa residues/turn stabilised by H bonds

  R groups on the outside

  Rigid cylinder shape, acts as architectural support for protein
• What are the H bonds in an alpha helix formed between?

  Between the carbonyl-O & H of N-H from every 4th peptide
• What is an alpha helix formed by?

  By H bonds in same polypeptide chain (backbone, not side chains)
• What are the 4 levels of protein structure?

  Primary- sequence of aa in peptide chain

  Secondary- folding/coiling of peptide chain (usually into alpha-helix or beta-pleated sheet)

  Tertiary- peptide chain folds upon itself

  Quaternary- folded peptide chains join together
• What is meant by the 'direction of polypeptides'?

  The first aa has a NH3+ group (-N-terminal end)

  The last aa has a COO- group (-C- terminal end)
• What are some features of a peptide bond?

  Shorter than expected C-N bond length

  Rigid C-N bond, no rotation, trans arrangement of groups (R groups alternate from top to bottom)

  Partial -ve charge on O atoms, partial +ve charge on N atom

  Peptides can form H bonds with other polar groups (including other peptide bonds) in the polypeptide chain (e.g. alpha-helix)
• What is required for the peptide bond to form and be broken?

  To form: the aa undergo dehydration synthesis which is an enzyme reaction & the bond is very strong

  To break it: hydrolysis takes place which will only be done by enzyme (lysosome)
• What is special about histidine at physiological pH?

  It can easily gain or lose its proton
• What happens when positively charged side chains are taken out of pH 7 and placed in higher pHs?

  In a higher pH (e.g. pH 13), they lose that extra proton
• What happens when negatively charged side chains are taken out of pH 7 and placed in lower pHs?

  In a lower pH (e.g. pH 2), they gain that proton back
• What does polar mean?

  Uneven positioning of electron pairs in covalent bonds between atoms of different electronegativities
• Compare the side chains of the amino acids at pH 7.

  Aspartic & glutamic acid have a -ve side chain

  Arg, Lys & His have a +ve side chain

  Asn, Gln, Ser, Thr & Tyr all have uncharged polar side chains

  The rest are non-polar
• What is different about histidine & arginine compared to the other amino acids?

  They are bases
• What is the R group in arginine?

  
• What is the R group in histidine?

  
• What is the R group in cysteine?

  
• What is the R group in glutamic acid?

  
• What is the R group in glutamine?

  
• What is the R group in aspartic acid?

  
• What is the R group in asparagine?

  
• What is the R group in phenylalanine?

  
• What is the R group in alanine?

  
• What is the R group in glycine?

  
• Are side chains (R-groups) involved in peptide bonding?

  No
• What is the alpha-carbon in an amino acid?

  Central carbon
• What are some properties of amino acids and why do some of their properties differ?

  They're water soluble, electrically charged at a physiological pH (7), meaning it's a zwitterion. Their properties differ depending on the R-groupSee an expert-written answer!We have an expert-written solution to this problem!
• What does the folded conformation of a protein in an aqueous environment consist of?

  A hydrophobic core region containing non-polar side chains whilst the outside of the molecule contains polar side chains, enabling them to form hydrogen bonds
• What does a protein's function depend on?

  Its 3-D structure, which depends on its linear structure