Biologically Important Molecules III – Proteins

Question 1

What is primary structure of protein ?

Answer 1

the sequence of amino acid residues

Question 2

What is secondary structure of protein ?

Answer 2

The localised conformation of the polypeptide backbone; stabilised by hydrogen bonds
-only considers backbone of polypeptide

Three types:
-⍺ helix
-β strands and sheets
-Triple helix

Question 3

What is tertiary structure of protein ?

Answer 3

the three-dimensional structure of an entire polypeptide, including all its side chains
-Arrangement of all atoms of a polypeptide in space
-Consists of local regions with distinct secondary structure

Question 4

What is quaternary structure of protein ?

Answer 4

the spatial arrangement of polypeptide chains in a protein with multiple subunits

Question 5

How can polypeptides rotate ?

Answer 5

Polypeptides can rotate around the angles between:
-The a carbon and the amino group
-The a carbon and the carboxyl group

Question 6

Describe alpha helices

Answer 6

Type of secondary protein structure
-Rod-like, mostly right-handed helix
-Made of a single polypeptide chain
-Stabilised by hydrogen bonds form between the C=O group of one amino acid and the N–H group four residues ahead

Right handed: if looked down from top would corkscrew away from you clockwise

Question 7

How does proline disrupt α-helices?

Answer 7

Proline residues disrupt α-helices because their rigid ring structure prevents proper hydrogen bonding and backbone flexibility needed for the helix

Question 8

Describe beta sheets

Answer 8

Polypeptide backbone almost completely extended
Can involve different polypeptides or occur within a polypeptide
Can be parallel or antiparallel
Glycine and proline can allow strand to double back to form these sheets
Has a repeated ‘zigzag’ structure; also called beta pleated sheet

top is paralell

Question 9

What are triple helices ?

Answer 9

Characteristic of collagen; a major fibrous protein
-Water-insoluble fibres
-Three left-handed helical chains twisted around each other form a right-handed superhelix
-Polypeptide chain parallel
-Are mechanically strong

Repeating sequence of X-Y-Gly in all strands
-X = any amino acid
-Y = proline or hydroxyproline
-also contains hydroxylysine

Inter-chain H-bonds (no intra-chain)
-involving hydroxylysine and hydroxyproline

Covalent inter- and intra-molecular bonds

All of these are in reference to collagen

Question 10

What is collagen ?

Answer 10

Component of bone and connective tissue
-Most abundant protein in vertebrates
-Tropocollagen is formed by triple helix of individual chains
-Mechanically strong

Question 11

What are examples of tertiary structures ?

Answer 11

Fibrous proteins
Globular proteins

Question 12

What are fibrous proteins ?

Answer 12

Contain polypeptide chains organized approximately parallel along a single axis.
-Consist of long fibers or large sheets
-Tend to be mechanically strong
-Insoluble in water and dilute salt solutions
-Play important structural roles

Question 13

What are examples of fibrous proteins ?

Answer 13

Keratin; hair and wool
Collagen; connective tissue e.g. cartilage, bones, teeth, skin, and blood vessels

Question 14

What are globular proteins ?

Answer 14

Proteins which are folded to a more or less spherical shape
-Tend to be soluble in water and salt solutions
-Most of their polar side chains are on outside and interact with aqueous environments; hydrogen bonding and ion-dipole interactions
-Most of their nonpolar side chains are buried inside
-Nearly all have substantial sections of alpha-helix and beta-sheet
Examples are; myoglobin, haemoglobin

most enymes are globular

Hydrophillic outside and phobic inside is what forms globules

Question 15

Which forces stabilise tertiary structure ?

Answer 15

-Covalent disulphide bonds
-Electrostatic interactions (salt bridges)
-Hydrophobic interactions
-Hydrogen bonds (of backbone and side chain)
-Complex formation with metal ions

Question 16

How are disulphide bonds formed ?

Answer 16

Oxidation of cysteine to form bridghe
-Can be important regulators in proteins; vulnreable to oxidation and reduction

Only two cysteines can form disulphide bridge, methionine cannot

Question 17

Where are polar groups usually located on proteins ?

Answer 17

On the outside
-interact with water

Question 18

How does sickle cell anaemia arise ?

Answer 18

1) Single nucleotide sequence change in coding region of the b chain of haemoglobin A
2) Protein alterered with valine instead of glutamic acid
3) Under low O2 conditions, haemoglobin polymerises; rigid, sickle shape cells
4) Can block blood flow in capillaries

Change in amino acids can lead ot significant functional/structural changes

Question 19

Describe how errors in protein folding can arise and what this can lead to

Answer 19

Proteins may fold spontaneously into their correct shape; can be slow and erroneous;
-may begin to fold incorrectly before it is completely synthesised
-may associate with other proteins before it is folded properly
examples: Alzheimer’s, Parkinson’s, CJD

Question 20

What is protien folding sometimes aided by ?

Answer 20

Sometimes folding process is aided by other specialised proteins
chaperones

Question 21

Give examples of prion diseases

Answer 21

Mad cow disease
-caused by infection of prion which probs appeared spontaneously

Creutzfeldt-Jacob disease
-caused by spontaneous (mainly) or inherited mutations

Human can get CJD by eating MCD beef, especially near brain/nervous tissue

Question 22

What are prions ?

Answer 22

Proteinaceous infectious agent
-Normal conformation PrP^c; disease-causing form PrP^Sc
-Diseased form has loads of beta-sheets and aggregates into multimeric complexes; resistant to degradation
-Spontaneous refolding is extremely rare
-Presence of PrPSc acts as a template for misforming of native prion proteins

PrP^c is the prion protein

Question 23

How can protein structure be disrupted and the protein denatured ?

Answer 23

Heat; increase in vibrations in a protein
Extremes of pH; electrostatic interactions interrupted
Detergents, urea, guanidine hydrochloride; disrupt hydrophobic interactions
Thiol agents, reducing agents; reduce and thereby disrupt disulphide bonds

Question 24

Describe the tertirary structure of myoglobin

Answer 24

Globular protein
-Contains a haem prosthetic group, which contains an iron Fe(II) ion.
-Haem group binds oxygen; one oxygen molecule per myoglobin protein
-Stores oxygen in muscle

1 haem per myoglobin, does not have a quaternary structure

Question 25

Describe the quaternary structure of haemoglobin

Answer 25

Has four subunits; two alpha and two beta chains -Each subunit contains a haem group and can bind one oxygen molecule -Binding of one oxygen changes affinity of the other subunits; allosteric regulation -Transports oxygen in blood

Question 26

How can protein conformation be changed

Answer 26

Changes in protein conformation can arise from redox interactions that affect the state of metal ion centres or disulphide bridges, and also through electrostatic interactions, salt bridging and hydrophobic interactions.

Question 27

What is tropocollagen ?

Answer 27

-Structural unit of a collagen fibre -Three helical chains twisted around each other to form a right-handed superhelix -Interchain H-bonds and intermolecular covalent bonds | Collagen triple helix is a quaternary structure ## Footnote The individual chains are helical, and the triple helix is the right-handed superhelix