THEME 3 MOD 4

Question 1

Why is protein diversity significant?

Answer 1

one gene can code for more than one protein, helping explain the diversity of the proteome compared to the genome

Question 2

how might protein activity be controlled

Answer 2

post transcriptional (alternate splicing) and post translational mods

Question 3

What is a proteome?

Answer 3

full number of protein expressed by dna

Question 4

Genome vs Proteome

Answer 4

genome has 20-25,000 protein coding genes, where splicing/ rna modifications and post translational mods contribute to over 1 million different proteins in our proteome

Question 5

Where do mature mRNAs go?

Answer 5

transported out of the nucleus to the cytosol where free or ER bound ribosomes induce translation

Question 6

Can the composition of our proteome change?

Answer 6

Yes. Our proteome can change is response to signals during development as well as internal and external cues. These changes stimulate cellular responses

Question 7

What are some post translational modifications

Answer 7

cleavage, disulphide bonding, folding, covalent attachments of other molecules, degradation of entire proteins

Question 8

what are the different forms of covalent attachment of molecules and how do they work

Answer 8

• phosphorylation (reversable): covalent attachment of a phosphate group to serine, threonine or tyrosine amino acid residues. facilitated by kinases (enzymes)
• Methylation: covalent attachment of methyl groups to a protein
  -acetylation: covalent attachment of acetyl group to specific aa residue in a protein

Question 9

Stimulus example

Answer 9

increase in blood glucose levels

Question 10

explain the process of cellular responses when blood glucose levels is increased.

Answer 10

1. glucose absorbed into bloodstream: through thin epithelial surfaces in the mouth and through the microvilli of small intestine
2. pancreatic beta islet cells detect the increased glucose levels.
3. beta islet cells adjust the amount of synthesis and secretion of insulin protein
4. insulin effector proteins bind to receptor monomers (which fall into family of receptor kinases) on target tissues.
5. conformational change of insulin binding to receprots causes the monomers to pair up (dimerize).
6. cytoplasmic domains of the receptors act like kinase proteins and phosphorylate each other at many points along the receptor tails, causing other cytoplasmic proteins to bind or react
7. The cytoplasmic proteins activate a series of transducer and amplifier proteins through a cellular signaling cascade regulated by positive feedback loops to keep signal and amplification on
8. glucose transporter proteins are activated by the intracellular amplified signal to take up glucose into the cell.
9. negative feedback loops terminate an intracellular signal. double negative feedback loops inhibit the inhibitor of the signal.
10. drop in blood glucose will be detected by pancreatic cells and the pancreatic cells will decrease secretion of insulin and sensor cells response is also inhibited.

Question 11

significance of insulin biosynthesis

Answer 11

insulin levels can be regulated at transcriptional and translation levels. insulin biosynthesis is effected by increased blood glucose, as insulin gene transcription and mrna translation are increased during this time

Question 12

significance of rough er in relation to insulin

Answer 12

rough er synthesizes/ produces insulin protein

Question 13

who is Dorothy Hodgkin

Answer 13

an xray crystallographer who determined the functional structure of the insulin protein: two amino acid chains, an alpha chain of 21 amino acids and a beta chain made up of 30 amino acids, the two chains form a dimer

Question 14

What post translational modifications result in the functional insulin protein.

Answer 14

preproinsulin: contains n-terminal signal sequence recognized by signal recognition particles (SRPs) which facilitates translocation of preproinsulin into lumen of rough ER where terminal signal sequence in cleaved
proinsulin: accurately folds by assistance of chaperone proteins and 3 disulphide bonds form. proinsulin transported to golgi apparatus where c chain is cleaved

Question 15

Describe protein receptors structural signifigance

Answer 15

receive and interpret information from signal proteins

thousands of cell receptors with ability to bind specific signals or ligands to elicit a cellular response

receptor kinases are a family of receptor proteins that exist in monomeric forms

Question 16

what cells uptake glucose

Answer 16

adipose cells: uptake glucose with fatty acids to store as triglycerides

liver and muscle cells: take up glucose and store it as glycogen

Question 17

what is alternate splicing and what does it do?

Answer 17

splicing of pre mrna at different junctions to create different mrna isoforms that code for different protein products.

during alt splicing some exons may be included in some mature mrna and not others

alt splicing can occur within the same cell or different cells

Question 18

are insulin receptors a product of alternate splicing. why or why not

Answer 18

yes they are:

insulin receptor pre mrna has 22 exons

in skeletal muscle exon 11 is removed, and skeletal muscle insulin receptors isoforms have a higher insulin affinity in their receptors which is beneficial to meet the high energy demands of muscle cells

in liver cells receptor proteins exon 11 is present in the mrna isoform transcript, as a result liver cells have a lower insulin affinity

Question 19

disease related to faulty alt splicing or post translational mods

Answer 19

improper post translational modifications of insulin protein would result in an ineffective effector/signaling protein

defect in the insulin protein or insulin receptor because of post translational or alternate splicing errors can cause an inability to take up glucose, resulting in hyperglycemia and diabetes