Protein structure and function

Question 1

What are amino acids?

Answer 1

small molecules that are building blocks of proteins
20 common natural amino acids

Question 2

What do amino acids exist as at neutral pH?

Answer 2

zwitterions

Question 3

How is property of amino acids determined?

Answer 3

• side chain

Question 4

What are peptides?

Answer 4

Two or more amino acids linked by a peptide bond

Question 5

What are proteins?

Answer 5

Large biomolecules comprised of one or more long chains of amino acid residues
Polypeptide= protein
Each amino acid unit in polypeptide= residue

Question 6

What is the primary structure of a protein?

Answer 6

• Linear sequence of amino acids encoded by DNA
• Defines how the protein will fold and function
• Single change in amino acid structure can cause disease

Question 7

What is the secondary structure?

Answer 7

Hydrogen bonds between aa form stable structural elements
Alpha helices
Beta pleated sheets

Question 8

What influences the conformations of each polypeptide chain?

Answer 8

Limitations in bond length
Bond angle

Question 9

What is an alpha helix?

Answer 9

Coiled structure stabilised by intrachain hydrogen bonds

Question 10

What is Proline?

Answer 10

Helix breaker
Ring structure does not allow for 100 degree rotation
No H-bond donor

Question 11

What are the 5 common amino acids (MARKL)

Answer 11

Methionine
Alanine
Arginine
Lysine
Leucine

Question 12

What are beta sheets?

Answer 12

Are stabilised by hydrogen bonds between strands
Polypeptide chains can change direction by making reverse turns and loops

Question 13

What is the tertiary and quaternary structure?

Answer 13

To function many proteins fold into a compact, globular shape= tertiary structure
When two or more polypeptide chains come together to give a functional molecule= quaternary structure

Question 14

What holds together tertiary and quaternary structures?

Answer 14

H-bonds
Ionic interactions
Disulfide bonds
Van der waals
Hydrophobic interactions

Question 15

What are hydrogen bonds?

Answer 15

between hydrogen atom (covalently bound to a proton donor) and a proton acceptor

Question 16

What are ionic interactions?

Answer 16

between charged amino acids, often found surface exposed

Question 17

What are disulfide bonds?

Answer 17

Between cysteine residues

Question 18

What are van der waals interactions?

Answer 18

weak electrostatic forces

Question 19

What are hydrophobic interactions?

Answer 19

between hydrophobic residues, often form on the inside of proteins

Question 20

What does protein diversity mean?

Answer 20

Diversity in protein structure means proteins can have a large number of functions in the cell

Question 21

What are 5 protein functions?

Answer 21

Structural
Regulatory
Carriers
Catalytic
Sensory

Question 22

What is protein trafficking?

Answer 22

the mechanism by which a cell transports proteins to the appropriate locations either inside or outside the cell

Question 23

Why is correct trafficking essential?

Answer 23

Incorrect= disease

Question 24

Where are proteins synthesised?

Answer 24

On ribosomes bound to ER or on free ribosomes

Question 25

What is the cytosolic pathway?

Answer 25

-By default, proteins synthesised on free ribosomes remain in cytosol -For import into nucleus they have nuclear localisation signal (allows them to be recognised and transported through the nuclear pores) - For import into mitochondria, have N-terminal mitochondrial import sequence

Question 26

What is the secretory pathway?

Answer 26

Proteins for secretory pathway have: N-terminal signal sequence 8-10 hydrophobic amino acids Proteins synthesised on ER-bound ribosomes will be secreted from the cell unless they contain addition localisation signals

Question 27

What happens when N-terminal signal sequence is translated?

Answer 27

- Recognised by SRP (signal recognition particle), which binds to SRP receptor on ER and recruits ribosome to ER membrane Nascent polypeptide chain is then translocated into the ER lumen

Question 28

What happens to soluble proteins?

Answer 28

N-terminal signal cleaved Secreted into vesicles

Question 29

What happens to proteins with more un-soluble regions?

Answer 29

Additional localisation signals allow membrane proteins to be folded into the ER or other membrane bound organelles (plasma membrane) Uncleaved

Question 30

What are post- translational modifications (PTMs)?

Answer 30

A process of changing one or more amino acids in a protein after translation 50 types Can alter function, cell location & viability

Question 31

What are the most commons PTMs?

Answer 31

Phosphorylation and dephosphorylation

Question 32

What is phosphorylation?

Answer 32

Addition of a phosphate group At serine, threonine or tyrosine

Question 33

What can phosphorylation do?

Answer 33

Alter protein function and enable cell signalling Occurs throughout the cell

Question 34

What is the PTM glycosylation?

Answer 34

- Attach carbohydrate - O-linked at serine or threonine (simple) - N-linked at asparagine (complex_ - Occurs in ER & Golgi

Question 35

What can glycosylation do?

Answer 35

- Increase protein stability - Help protein folding - Modulate protein function, protein- ligand interactions - Aid in cell attachment to extracellular matrix - Block pathogens from attacking host cells

Question 36

What is the PTM UBIQUITINATION?

Answer 36

Three step enzymatic cascade involving E1, E2, E3 enzymes Transfers ubiquitin, via its c-terminal glycine, onto the amino acid group of a lysine residue of the substrate

Question 37

What does ubiquitination cause?

Answer 37

Different forms code for different functions Large role in targeting proteins for proteasomal degradation Occurs in multiple locations in the cell

Question 38

What is protein misfolding?

Answer 38

Correct protein folding crucial for function Incorrect can lead to disease Misfolding can happen due to change in primary sequence or escape from the native folding pathway

Question 39

What is prion disease?

Answer 39

Fatal neurodegenerative diseases Transmissible spongiform encephalopatjoes

Question 40

What is a prion?

Answer 40

Misfolded protein that induces misfolding in normal variants of the same protein Leads to accumulation of prion protein aggregates and cell death

Question 41

How does prion disease originate?

Answer 41

Sporadically, by transmisson or in heritance

Question 42

What is amyloidosis?

Answer 42

misfolding of amyloid protein results in formation of fibrils with cross beta structure that cannot be degraded

Question 43

What is alzheimer's disease?

Answer 43

Age related neurodegenerative disease, affects memory, thinking and behaviour

Question 44

What is alzheimers disease characterised by?

Answer 44

- Extracellular accumlation of amyloid- beta peptides as amyloid plaques - Aggregation of abnomally- phosphorylated tau protein into intraneuronal neurofibrillary tangles

Question 45

What does Tau protein normally do?

Answer 45

- Stabilises microtubules - Microtubules are essential for intercellular transport and neuronal structure - Excessive or abnormal phosphorylation of tau leads to oligomerisation and tangle formation= microtubule destabilisation