protein targeting

Question 1

give an example of a disease with a mutation in the nuclear localising signal

Answer 1

swyer syndrome

loss/mutation in the NLS for transcription factor for SRY protein

XY genotype but look female

SRY required for testis differentiation

Question 2

Give an example of a disease with mutation affecting protein import to mitochondria

Answer 2

pyruvate dehydrogenase deficiency

mutation in PDH of arg to proline
proline is positively charged and a helix breaker and may destabilise the helical N-terminus and signal is not recognised

Question 3

Give an example of a disease affecting transport of proteins to lysosomes

Answer 3

N-acetyl glucosamine phosphotransferase and phosphodiesterase are needed in the addition of mannose - 6 phosphate to a lysosomal enzyme

I-Cell disease is a fatal inherited condition with a deficiency in N-acetyl glucosamine phosphotransferase

lysosomes become bloated with undegraded material

Question 4

Give the function of the ER

Answer 4

insertion of proteins into membranes
specific proteolytic cleavage 
glycosylation 
formation fo S-S bonds 
proper folding of proteisn 
assembly of multisubunit proteins 
hydroxylation fo secreted lysine and proline residues

Question 5

why is glycosyslation of proteins so important and where does it occur?

Answer 5

in the ER

ensures correct protien folding
protein stability
facilitates interactions with other molecules e.g. adhesions
deficiencies in N-linked glycosylation cna lead to severe inherited human disease

Question 6

Give some examples of proteins secreted ini a constitutive pathway or regulated pathway

Answer 6

constitutive - collagen, albumin, immunoglobulins, prohormones and receptors

regulated - insulin, glucagon, beta endrophins, alpha - MSH, ACTH and trypsin

Question 7

Give the synthesis and secretion of collagen

Answer 7

C - cleavage of signal peptide by signal pepsidase forming pro alpha chains from prepro
H - hydroxylation of proline and lysine residues
A - addition of oligosaccharides in N- linked glycosyslation
D - disulphide bond formation
T - triple helix formaiton
O - o linked glycosylation in golgi
G - golgi body secretion
I - inot extracellular matrix
R - removal of N and C terminal propeptides
L - lateral association with cross linking by lysyl oxidase

Question 8

give three important enzymes in the formation of collagen and which one can be deficient to give stretchy skin

Answer 8

signal pepsidase
prolyl hydroxylase
lysyl oxidase

lysyl oxidase can be deficient