Lecture 6 - Protein Folding

Question 1

What is Supersecondary structures?

Answer 1

Elements of secondary strucutre i.e helices and strands are connected by turns or regions of less ordered strucutre called loops or coils to make up Supersecondary structure

Question 2

Common motifs of Supersecondary strucutre

Answer 2

• helix - turn - helix
• beta hairpin
• Greek key
• strand-helix strand

Question 3

What is a helix-turn-helix

Answer 3

• Supersecondary structure
• two helix connected by a turn (polypeptide sequence that causes a change in direction - 4 residues)
  E.G: found in:
• DNA binding protiens
• Calcium binding proteins

Question 4

EF-hand proteins

Answer 4

Question 5

B-hairpin

Answer 5

• common
• antiparralel
• length varies

Two examples:
- bovine pancreatic trypsin inhibitor
- snake venom toxin

Question 6

Greek key

Answer 6

• 4 antiparalalel strands
• 4 beta strand connected by loops and turns

Question 7

The Greek key as one long, bent hairpin

Answer 7

Question 8

Strand, helix, strand

Answer 8

• alpha helix sits just below or just above the beta strands
• parallel beta strands - hydrogen bonds

Question 9

Protien domains

Answer 9

• Supersecondary structure elements combine to form domains
• independently folded regions that often possess a specific function within the protien
• hydrophobic core (very important for protein stability)
• hydrophobic parts are arranged on the surface in contact or near solvent
• small protiens contain usually one domain, larger protiens may have multiple domains

Question 10

Tertiary structure families

Answer 10

a domain family
a/B family
Antiparralel B family

Question 11

How to form a protien domain

Answer 11

• Supersecondary stucture elements combine

Question 12

Structure of protein domains

Answer 12

• independently folded regions that often possesses a specific function within the protein
• hydrophobic core (very important for protein stability)
• hydrophilic parts are arranged on the surface in contact or neat solvent
• small protiens contain usually one domain
• larger proteins contain multiple domains

Question 13

A-domain family is mainly___

Answer 13

Helical

Question 14

a-domain family - four helix bundle

Answer 14

• amphipathic helices with side-chains packed closely together within a hydrophobic core

Question 15

a-domai family - globin fold

Answer 15

• amphiathic helices with side-chains packed closely together within a hydrophobic core
• packing can occur between no adjacent helices

Question 16

What is a/B family a mix of

Answer 16

A mix of a and B strucutre

Question 17

a/B barrel

Answer 17

Question 18

a/B family - horseshoe fold

Answer 18

16 stand - helix motif repeats

Question 19

Anti-parallel B family consists of..

Answer 19

Mostly antiparallel B strucutre

Question 20

Anti-parallel B family

Answer 20

• anti-parallel B barrel - retinol binding protein
• hydrophobic inside of barrel

Question 21

Many more families of protien strucutre exist

Answer 21

Yep

Question 22

In _____ common _____ ______ are repeated and ______ to make different types of ______

Answer 22

In nature common structural domains are repeated and combined to make different types of proteins

Question 23

_____ are often ‘_____’ by nature and combined with other domains to make proteins with different _____

Answer 23

Domains are often ‘reused; by nature and combines with other domains to make proteins with different functions

Question 24

Common protein domains

Answer 24

Question 25

Proteins are…

Answer 25

… synthethsised as linear polymers that must fold into a 3D functional structure

Question 26

Where are proteins made and what happens after they are made

Answer 26

- protein is made at the ribosome - and then generally they fold into their active shape spontaneously

Question 27

Where are the instructions needed for protien folding

Answer 27

The only “instructions” needed are embedded in the amino acid sequence

Question 28

The Anfinsen experiment in a nutshell

Answer 28

In absence of everything apart from a string of amino acids - it reforms itself

Question 29

Protein folding directed largely by…

Answer 29

…its internal hydrophobic residues, which form an internal hydrophobic core, while hydrophobic residues are solvent exposed

Question 30

Likely folding pathway sequence

Answer 30

1. Formation of short secondary strucutre segments 2. Subdomains form 3. Subdomains come together to form a partly folded domain; a “molten globule” that can rearrange, (tertiary strucutre still partly disordered) 4. Final domain strucutre emerges, small conformational adjustments to give final compact native structure

Question 31

Stabilisation of protein folding

Answer 31

- non-covalent interactions - individually weak in proteins, collectively make a significant contribution to protein conformational stablility - in some proteins additional covalent bonds (e.g disulfide binds) may be present that contribute to conformation stability - the hydrophobic core is likely the most important non covalent contributor to protein stability in aqueous soluation

Question 32

3 ways it can fold

Answer 32

1. Chaperone-independent 2. Chaperone-depended e.g Hsp70 3. Chaperoning-dependent e.g GroEL-GroES

Question 33

Unfolding proteins occurs if the non-covalent bonds break due to…

Answer 33

- change in pH - heating (kinetic energy) - more

Question 34

If you change the side chains - not going to face the same properties - heat cause bonds to vibrate breaking hydrogen bonds

Answer 34

If you change the side chains - not going to face the same properties - heat cause bonds to vibrate breaking hydrogen bonds

Question 35

Can protiens in living orgasnisms that are folded normally sometimes change their shape and become misfolded?

Answer 35

Yes

Question 36

Some misfolded proteins can ______ other _____ to change their _____ as well, sometimes with ________ ___________

Answer 36

Some misfolded proteins can cause other proteins to change their shape as well, sometimes with disastrous consequences

Question 37

How do prion diseases form

Answer 37

- prp changes its shape and form aggregates that cause Brian damage

Question 38

Prion diseases include

Answer 38

- Bovine spongiform encephalopathy (BSE) - Creutzfeldt-Jacob disease - Kuru

Question 39

What is a prion

Answer 39

- the protiens that cause the problem are called prions for “protiens infections agent”

Question 40

The abnormal form of a prion protein induces the normal form of this protein to become misfolded

Answer 40

The abnormal form of a prion protien induces the normal form of this protien to become misfolded

Question 41

What transformation does prion disease induce

Answer 41

A —-> B transformation

Question 42

Treatment for prion diseases

Answer 42

- no treatment available - always fatal

Question 43

Model for prion conformation

Answer 43

Question 44

Diseases which protein misfolding or aggregation is THOUGHT to contribute to

Answer 44

- alzheimers disease - type two diabetes - prions are not involved in these ailments - abnormally folded protien called amyloid is thought to contribute

Question 45

All the _____ required for a protein to ___ is in the ____ _____ of _____ _______

Answer 45

All the requires information requires for a protein to fold is in the primary sequence of amino acids

Question 46

A domain is….

Answer 46

An independently folded region of a protien, often with a specific role, and usually with a hydrophobic core

Question 47

The tertiary strucutre of a protein is largely stabilised by…

Answer 47

…non-covalent interactions

Question 48

Protien misfiling can lead to..

Answer 48

Disease