Lec 5 and 6: Proteins (Structure and Function)

Question 1

what are proteins?

Answer 1

Fundamental cellular component vital for all cellular functions

Question 2

state the function and give an example for each protein type;

structural, storage, transport, hormonal, receptor, contractile, defensive, enzymatic

Answer 2

Question 3

what is a polypeptide?

Answer 3

Amino acid monomers linked together by peptide bonds

Question 4

what do more than 40 amino acids form?

Answer 4

a protein!!

Question 5

how does the sequence of the amino acids effect the structure and therefore function of a protein?

Answer 5

• different sequence of amino acids
• dfferent primary structure
• different folding and coiling of the beta pleated sheet and coiling of the alpha helix
• different tertiary struture so the folding of the protein is different
• different different 3D shape, active site is different also
• substrate can not fit into the active site, enzyme no longer works

Question 6

how many standard amino acids are there? what is the name given to these amino acids?

Answer 6

20

proteinogenic amino acids

Question 7

which enantomer is more dominate?

Answer 7

L enantiomers

(D is very rare)

Question 8

what happens to a zwitter ion when an acid or base is added?

Answer 8

in acid: the carboxyl group gains a hydrogen

in alkali: amino group loses an hydrogen

Question 9

what type of physicochemical properties (4) can the R group on the amino acid be?

state how many out of the 20 are each of this property

Answer 9

Nonpolar (9) Hydrophobic (“water-hating”)

Polar (6)

Acidic (2)

Basic (3)

(polar, acidic and basic are hydrophillic)

Question 10

which are the non polar amino acids?

Answer 10

glycine (Gly)

alanine (Ala)

valine (Val)

leucine (Leu)

isoluecine (Ile)

methionine (Met)

phenylalanine (Phe)

tryptophan (Trp)

prolive (Pro)

Question 11

out of the non polar amino acids which one has a non chiral centre?

Answer 11

glycine

Question 12

out of the non-polar amino acid which one is not a primary amino acid?

Answer 12

proline

Question 13

which are the acidic amino acids?

at what pH are their sides chain negatively charged?

Answer 13

Aspartic acid (Asp)

Glutamic acid (Glu)

pH 7.4

Question 14

which are the basic amino acids?

at what pH are their sides chains positively charged?

Answer 14

lysine (Lys)

Arganine (Arg)

Histindine (His)

Question 15

which are the polar amino acids?

why are they polar?

Answer 15

Tyrosine (Tyr)

Asparagine (Asn)

Glutamine (Gln)

Serine (Ser)

Threonine (Thr)

Cysteine (Cys)

they are polar because they can form hydrogen bond interactions with similar side-chains and peptide bonds

Question 16

which amino acid can join together to form a disulphide bridge?

Answer 16

cysteine in a oxidation reaction

Question 17

how do amino acids link together and what bond does this form?

Answer 17

link at the carboxyl group of one amino a and an amino group of another amino a via dehydration synthesis

peptide bond is formed

Question 18

what does it mean by proteins are directional?

Answer 18

they are labelled from n (amino) terminus to c (carboxyl) terminus

Question 19

whay are cis amino acids rarer than trans?

which amino acid is an exception to this?

Answer 19

because the side chains are bulky if they are on the same side they clash and are less stable

glycine is an exception

Question 20

what is the significance of proline in the secondary structure of a protein?

Answer 20

proline disrupts α-helix structure (“helix breaker”)

Question 21

in which proteins are alpha helices most/least abundant in?

Answer 21

• Abundant in haemoglobin
• Absent in chymotrypsin (digestive enzyme)

Question 22

what is meant by amphipathic?

Answer 22

has a hyrdophobic and hydrophillic parts

Question 23

which is more flexible? alpha helices or beta pleated sheets?

Answer 23

b-sheeets more flexible because they have a greater distance between the amino acids

Question 24

can beta pleated sheet to be amphiphatic?

Answer 24

yes they can

you have the plane of beta sheets and the above bed and below bed of side chains

Question 25

what are loops and radom coils usually part of?

Answer 25

enzyme active site

Question 26

what are structural motifs?

Answer 26

Arrangements of 2° structures (super-secondary structures) that occur frequently within a protein and can be associated with a specific biological function

Question 27

what are the type of structural motifs (6)?

Answer 27

- β-Hairpin – Helix-loop-helix – Greek key – Coiled coil – Zinc finger – Beta barrel

Question 28

what is a β-Hairpin motif? what is most common in?

Answer 28

= Two adjacent anti-parallel β strands joined by a hairpin loop most common in globular proteins

Question 29

what is a Helix-loop-helix motif? what is it most common in and what is it's function?

Answer 29

Helix-loop-helix motif most common in; transcription factors cell signalling proteins function: DNA-binding Ca2+-binding

Question 30

what is a greek key motif? what is it most common in?

Answer 30

Three anti-parallel β-strands connected by hairpins plus a 4th strand which is adjacent to the 1st and linked to the 3rd by a longer loop Common in a range of proteins (e.g. proteases [trypsin], cytokines [TNFα])

Question 31

what is a coiled coil motif? give examples of proteins that contain this motif

Answer 31

Usually contain repeats of a 7 residue pattern (hxxhcxc) h=hydrophobic, c=charged, x=any Resulting amphipathic α-helices have a “stripe” of hydrophobic residues that coil around similar stripes in other helices such that hydrophilic residues project outwards Leu zippers in transcription factors [e.g. c-Fos] Structural proteins [Myosins]

Question 32

what is a zin finger motif? in which proteins is it most common? what is its function?

Answer 32

=Two anti-parallel β-sheets followed by 1 α-helix, stabilised by a zinc ion Common motif in many proteins including transcription factors Example: Kruppel-like factor 4 (KLF4) Functions: Binding of DNA, RNA, lipid and protein substrates

Question 33

what are beta barrel motifs? what are the 4 type of beta barrel motifs? what are they most common in?

Answer 33

Multiple anti-parallel β-sheets that twist and to form a closed structure First strand is hydrogen bonded to the last 4 types: Greek key barrel Up-and-down barrel Jelly roll barrel (complex) Beta-helix barrel most common in water channels (aqauporins)

Question 34

what are domains and what are they formed from? give an example

Answer 34

A polypeptide chain (or part of chain) that folds independently into a stable structure with its own hydrophobic core Formed from several simple motifs and secondary structure elements e.g Src homology 2 (SH2) domain – binds phospho-Tyr residues, important in insulin signalling

Question 35

which bonds occur in the tertiary structure?

Answer 35

– Hydrogen bonds = Between R Groups – Ionic bonds (=electrostatic attraction) = Between CO2- and NH3+ of R Groups – Disulphide bridges (=covalent crosslinks) = Between cysteine –SH groups (Cys-S—S-Cys) – Hydrophobic interactions = Hydrophobic R Groups cluster inside proteins to shield themselves from water

Question 36

which linkage is the strongest in the tertiarty structure?

Answer 36

disulphide bridge

Question 37

what are examples of fibrous proteins? what are the functions

Answer 37

fibrous proteins provide support and strength Collagen Keratins; α-keratins – Mammalian hair and nails β-keratins – Invertebrate silks, reptile scales, claws – Avian feathers, beaks and claws

Question 38

are fibrous proteins insoluble or soluble in water

Answer 38

insoluble

Question 39

what makes up collagen?

Answer 39

super helices of Gly-rich triple α-helices (=tropocollagen) that assemble into fibrils

Question 40

what is the function of collagen?

Answer 40

collagen is the main protein in connective tissure so itsupports, connects or separates tissues and organs

Question 41

what are α-Keratins made up of?

Answer 41

Composed of coiled-coils of two α-helices that assemble together into larger fibres

Question 42

what are the properties of α-keratins?

Answer 42

Strong and inextensible Insoluble and chemically inert because Disulphide bridges cross link coiled-coils making it very stable also

Question 43

what is an example of β-Keratins?

Answer 43

fibroin

Question 44

what is fibroin? what is it made up of and why is stretchy?

Answer 44

Fibroin is found in silk and spider webs Layers of anti-parallel β-sheets rich in Ala and Gly residues Sheets joined by amorphous stretches which confer elasticity and strength

Question 45

what are globular proteins? give examples

Answer 45

Mixture of irregularly folded 20 elements to form a compact 3-D shape e.g Myoglobin Haemoglobin Immunoglobulins

Question 46

what describe the structure and function of haemoglobin

Answer 46

it is a tetramer 4 polypeptide chains/subunits (α2β2 = adult haemoglobin) 4 haem molecules (haem = porphyrin ring +Fe2+ , binds O2) function: Transports O2 from lungs to the rest of the body Releases O2 to permit aerobic respiration to provide energy

Question 47

what is myoglobin?

Answer 47

related to haemoglobin, exists as single polypeptide

Question 48

what diseases are related to the mutation of haemoglobin genes?

Answer 48

Sickle cell disease: caused by a "non-sense mutation = changes primary sequence" – resulting in Change in RBC shape (sickle-shaped cells) – RBCs rigid, become blocked in capillaries Ischaemia/Organ Damage/Pain – Increased haemolysis (=RBC destruction) Anaemia/Spleen damage Thalassaemias

Question 49

what are immunoglobins? what are they made up of?

Answer 49

Y-shaped proteins of the immune system which identify and combat invading foreign organisms made up of: 4 chains linked by disulphide bridges – 2 large H (heavy) chains – 2 short L (light) chains -disulphide bonds variable region: form specific binding sites for non-self targets constant region: acts as marker for other components of the immune system

Question 50

what is meant by the denaturation of proteins?

Answer 50

Process in which proteins lose quaternary, tertiary and secondary structure present in their native state due to a change in environment resulting in loss of function

Question 51

how can pH cause denaturation? explain what happens in low and high pH

Answer 51

Ionic bonds very sensitive to pH: – Break ionic bonds – Disrupts tertiary structure – proteins become insoluble and precipitate out of water Low pH: high H+ conc H+ + COO- ---\> COOH High pH: low H+ conc NH3+ ---\> NH2 + H+

Question 52

how does high temperature cause denaturation?

Answer 52

Increase in temp vibrates and breaks H and ionic bonds proteins become insoluble and precipitate out of water

Question 53

what is pyrexia?

Answer 53

increased body temperature (fever) due to anti-viral defence mechanism

Question 54

how do solvents cause denaturation? which one specifically cause denaturation?

Answer 54

* Ethanol, acetone, phenol (organic solvents) * Forms new H bonds with protein side chains and backbone * Disrupt intra- and inter-chain H bonds * Causes protein to unfold and denature

Question 55

do solvents cause proteins to become insoluble?

Answer 55

no because solvents dissolve the protein and renders it soluble