MVU3 PROTEIN FOLDING IN THE CELL -2

Question 1

what are similar amino acids?

Answer 1

same properties

Question 2

what does AA sequence similarity indicate?

Answer 2

evolutionary conservation

Question 3

what does homology suggest?

Answer 3

common structure or function

Question 4

what are polypeptides if they do not have any sequence similarity?

Answer 4

they are said to be divergent

Question 5

what are proteins of the same family?

Answer 5

set of proteins or domains that have homologous sequences and structures
often have related functions
organism can have several proteins from same family
proteins from family can be found in different organisms

Question 6

what interactions can the polypeptide backbone have?

Answer 6

hydrogen bonds and van der waals

Question 7

what is the importance of post translational modification (PTM)?

Answer 7

can be chemically modified after translation
contribute to proteomic diversity and complexity
essential for regulation and cellular signaling

Question 8

what are the different types of PTMs?

Answer 8

cleavage into smaller proteins by peptidases (trans membrane proteins)
covalent modification of N terminus
covalent modification of side chains (introducing functional groups to proteins)

Question 9

what are side chain modifications used for?

Answer 9

can change surface or conformation of a protein
can create or block a binding site for other proteins
used as switches, very fast

Question 10

what are those PTMs regulated by?

Answer 10

enzymes
regulated and reversible

Question 11

what are the main types of PTMs?

Answer 11

phosphorylation
methylation
acetylation
glycosylation
sumoylation
ubiquitination

Question 12

what is the major regulatory mechanism and what proportion of proteins undergo?

Answer 12

phosphorylation
30% of proteins get phosphorylated

Question 13

what group is phosphorylated?

Answer 13

the hydroxyl group

Question 14

what are the 3 amino acids that can undergo phosphorylation?

Answer 14

(S, T, Y) serine, threonine and tyrosine

Question 15

what does adding a phosphoryl group do to an amino acid?

Answer 15

changes the charge (from polar to negatively charged - can now do ionic and electrostatic interactions) and the size (makes it bigger)

Question 16

what are the enzymes that transfer phosphates from ATP?

Answer 16

kinases

Question 17

how many different kinds of kinases are there?

Answer 17

50, they are specific for side chain and surrounding peptide sequence

Question 18

what enzymes remove phosphate groups?

Answer 18

phosphatases

Question 19

what are the different kinase/phosphatase families?

Answer 19

Ser/Thr kinases/phosphatases
Tyr kinases/phosphatases
dual specificity (Ser/Thr and Tyr) kinases/phosphatases
serine and threonine are together because they have very similar structures

Question 20

what is acetylation of lysine and its effects

Answer 20

lysine is the only one that can be acetylate
it changes the polarity
done by lysine acetyltransferases (KATs) and deacetylases (KDACs)
used for signaling and metabolic effects

Question 21

what does histone acetylation mean for DNA transcription?

Answer 21

histone acetylation is a sign of active transcription

Question 22

what does the methylation of arginine and lysine involve?

Answer 22

addition of 1 or 2 methyl groups to the guanidino group
adds size

Question 23

what are the different degrees of methylation possible of lysine?

Answer 23

mono, di or trimethylated

Question 24

what enzymes are involved in the methylation of lysine?

Answer 24

lysine methyltransferases and lysine demethylases

Question 25

what does PTM binding play an important role in?

Answer 25

transcription regulation and DNA repair mechanisms provides new binding sites for proteins

Question 26

what does the folded structure of a protein depend on?

Answer 26

depends on hydrophobic interactions in the interior of the structure

Question 27

where are polar structures found

Answer 27

found on the outer surface

Question 28

what is the native conformation?

Answer 28

the completely folded conformation of a protein

Question 29

when does side chain modification take place?

Answer 29

takes place after folding is complete

Question 30

what are the interactions that contribute to folding?

Answer 30

hydrophobic interactions, hydrogen bonds, van der waals interactions, ionic bonds, disulfide bonds

Question 31

what determines the native structure of a protein?

Answer 31

the primary sequence of AA

Question 32

what is the native structure in terms of free energy?

Answer 32

minimal energy folding is thermodynamically favoured (negative delta G) folding is spontaneous but assissted

Question 33

what is involved between the primary sequence and the native conformation?

Answer 33

intermediates unfolded domains have no secondary or tertiary structure

Question 34

what stabilises the native conformation of a protein?

Answer 34

hydrophobic contacts

Question 35

what do some domains require to be stable?

Answer 35

require a ligand partner (a cofactor or another protein subunit)

Question 36

what can native states be in equilibrium with?

Answer 36

near native folding intermediates

Question 37

what is aggregations?

Answer 37

hydrophobic regions prefer to be in contact with other hydrophobic regions interactions between different unfolded proteins leads to insolubility neurodegenerative diseases

Question 38

what can lead to protein misfolding?

Answer 38

genetic mutation required ligand not available harmful environment conditions (heat) aging: decreased efficiency of protein quality control mechanism (loss of protein homeostasis)

Question 39

what are some genetic mutations that can lead to changes to polypeptide sequences?

Answer 39

AA substitution, insertion, deletion, premature sotp

Question 40

what can substitution to a similar amino acid lead to?

Answer 40

may lead to little or no effect

Question 41

what does substitution that greatly changes the AA properties lead to?

Answer 41

can disrupt the folding/function of the protein

Question 42

what are mutations in the KCNH2 gene and what do they lead to?

Answer 42

Phe to Ser (pathogenic) Ser to Leu (pathogenic) Asp to Asn (not pathogenic)

Question 43

what is protein homeostasis?

Answer 43

extensive network of components that acts to maintain proteins in the correct concentration, conformation and subcellular location, to cooperatively achieve the stability and functional features of the proteome

Question 44

how many genes encode for chaperones and what happens when you delete a gene?

Answer 44

400 genes deletion= cell death

Question 45

what do chaperones recognise?

Answer 45

exposed hydrophobic patches

Question 46

what do you switch out phospho serine for when you want to see the effects of phosphorylation of serine in a lab?

Answer 46

switch it out for aspartic acid (similar structure to phospho serine)

Question 47

what do you switch out serine for when you want to see what happens when its not phosphorylated?

Answer 47

switch serine out for alanine (alanine has a similar structure and doesn't have an OH groups so it will never have a negative charge)