Lecture 2: The polypeptide chain and the amino acid sequence of proteins Flashcards
Aim: - the primary structure of polypeptides - the peptide bond - hydrogen bonds
How is the primary structure formed?
- dehydration reaction between 2 amino acids ( removal of H2O)
- this reaction occurs on the ribosome of the cell
- peptide bonds formed ONE AT A TIME starting at the N-terminal
true or false, does the polypeptide chain have direction?
And indicate the direction from start to end
true
N-terminal to C- terminal
What does it mean by RESIDUE
- all units of a polypeptide chain are therefore amino acid residues
an individual amino acid
- after dehydration, what remains of each amino acid is called an amino acid residue
- therefore these are structures that LACK A HYDROGEN ATOM of the amino group (-NH-CHR-CO-)
- or the hydroxy moeity of the carboxyl group (NH2-CHR-CO-)
- or both
What are proteins?
- are polypeptides defines by amino acid sequence
- these sequences are specified by the DNA
- the amino acid sequence of a protein is also called the PRIMARY STRUCTURE
true or false, the primary structure dictates how a polypeptide will fold?
true
Why does primary structure dictate higher levels of polypeptide structure?
- due to the chemical nature of the backbone and side chain (R- groups) positioned along the chain
- each protein contains a defined sequence of amino acids containing all the information necessary for a protein to fold into its biologically active 3-D structure
true or false does the human myoglobin a.a sequence the same as a whales’?
true (Val, Leu, Ser, Glu,Gly, Asp..) - same # of amino acids - very similar sequence - same oxygen binding
What are the consequences of a mutation in the DNA?
- the amino acid sequence will be changed, thus the structure of the protein is altered, and possibly the function as well
Give an example of mutation in humans, and its consequences
SICKLE CELL ANEMIA
alteration of amino acid sequence for the gene which codes for the biconcave structure of hemoglobin, can alter it to become sickle shaped, thus causing sickle cell anemia
CYSTIC FIBROSIS
-mutation, resulting in defective channel protein CFTR, this impairment can prevent Na+ ions from exiting the cell into the lumen, thus eg. sweat tends to be very salty
How does sickle cell anemia occur? what base changes occur, and what amino acids are coded for instead? Why is this change harmful?
- ) single substitution resulting in a different amino acid in protein causes sickle cell disease (Glu - Val)
- ) inherited substitution of one amino acid
- ) substitution occurs on the 6th position on the polypeptide
- ) thus abnormal hemoglobin tends to crystallize, deforming some of the cells into a sickle shape
- ) a person who has sickle cell anemia will have a life punctuated by “sickle cell crises”.
- ) “sickle cell crises” occurs when the angular cells clog tiny blood vessels
In sickle cell anemia, which position on the polypeptide is substituted from Glu - Val?
6th position
What is the normal shape of hemoglobin?
biconcave
How many amino acids does hemoglobin have?
146 amino acids
what can be concluded from the similarity of the human and whale amino acid sequence for myoglobin?
amino acid sequences can indicate evolutionary relatedness eg. myoglobin
How does length of the polypeptide chain vary?
- often 200-400 residues
- sometimes > 1000 (collagen -skin)
How do polypeptides fold up?
- peptide bond delocalised double bond
- no rotation- the peptide unit is RIGID AND PLANAR and ALMOST ALWAYS TRANS
true or false is the peptide bond almost always trans?
true
What geometrical shape of the peptide unit?
planar
Where can’t the polypeptide rotate?
the peptide bond
Define torsion?
the action of twisting or the state of being twisted
Which bonds can be rotated in an amino acid? (torsion)
between :
N-Calpha
Calpha -C (carboxyl)
- this is because these bonds are SINGLE BONDS
Why do sickle cells crystallize?
remember from Glu- Val; in the 6th position
- their structure results in an exposed hydrophobic region
- this is because Valine is hydrophobic
- therefore valine will tend to aggregate with other neighboring cells’ exposed valine; as it tries to get “away” from the surrounding water.
- thus molecules crystallize into a fibre
- capacity to carry oxygen is reduced
- sickle cells are also sticky, thus they tend to block blood vessels
Why is the peptide bond important?
- for stability and structure of proteins
does the peptide bond exist as a resonance structure?
yes
- being a mixture of N-C and N=C bond
what does the resonance structure tell us about the peptide bond?
- that it has a partial double bond character
- there is no rotation about the peptide bond
- almost always trans ( Ca atoms from each amino acid are on opposite planes of the peptide bond)
What is the significance of the singly bonded terminal carbon and nitrogen atoms?
potentially gives rise to many different arrangements of the polypeptide
true or false, is it the localization of the pi electron orbitals over O-C-N which accounts for the partial double bond character of the C-N bond
true
What causes a given polypeptide to fold up to just one stable, biologically active structure?
- the planar peptide bonds limits the folding pattern of proteins as ROTATION CAN ONLY OCCUR AROUND N-Calpha and Calpha-C=O bonds
What does the secondary structures regular, repetitive backbone depend on?
- the formation of HYDROGEN BONDS
- between N-H and C=O groups of the polypeptide
What does a hydrogen bond involve?
- involves an interaction betweeen:
- an H atom ATTACHED to an electronegative donor (eg. atom D)
- and an electronegative acceptor atom (eg. atom A)
D-H——–A
