Lecture 6 - Protein Folding Flashcards
What is Supersecondary structures?
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
Common motifs of Supersecondary strucutre
- helix - turn - helix
- beta hairpin
- Greek key
- strand-helix strand
What is a helix-turn-helix
- 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
EF-hand proteins
B-hairpin
- common
- antiparralel
- length varies
Two examples:
- bovine pancreatic trypsin inhibitor
- snake venom toxin
Greek key
- 4 antiparalalel strands
- 4 beta strand connected by loops and turns
The Greek key as one long, bent hairpin
Strand, helix, strand
- alpha helix sits just below or just above the beta strands
- parallel beta strands - hydrogen bonds
Protien domains
- 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
Tertiary structure families
a domain family
a/B family
Antiparralel B family
How to form a protien domain
- Supersecondary stucture elements combine
Structure of protein domains
- 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
A-domain family is mainly___
Helical
a-domain family - four helix bundle
- amphipathic helices with side-chains packed closely together within a hydrophobic core
a-domai family - globin fold
- amphiathic helices with side-chains packed closely together within a hydrophobic core
- packing can occur between no adjacent helices
What is a/B family a mix of
A mix of a and B strucutre
a/B barrel
a/B family - horseshoe fold
16 stand - helix motif repeats
Anti-parallel B family consists of..
Mostly antiparallel B strucutre
Anti-parallel B family
- anti-parallel B barrel - retinol binding protein
- hydrophobic inside of barrel
Many more families of protien strucutre exist
Yep
In _____ common _____ ______ are repeated and ______ to make different types of ______
In nature common structural domains are repeated and combined to make different types of proteins
_____ are often ‘_____’ by nature and combined with other domains to make proteins with different _____
Domains are often ‘reused; by nature and combines with other domains to make proteins with different functions
Common protein domains
Proteins are…
… synthethsised as linear polymers that must fold into a 3D functional structure
Where are proteins made and what happens after they are made
- protein is made at the ribosome
- and then generally they fold into their active shape spontaneously
Where are the instructions needed for protien folding
The only “instructions” needed are embedded in the amino acid sequence
The Anfinsen experiment in a nutshell
In absence of everything apart from a string of amino acids - it reforms itself
Protein folding directed largely by…
…its internal hydrophobic residues, which form an internal hydrophobic core, while hydrophobic residues are solvent exposed
Likely folding pathway sequence
- Formation of short secondary strucutre segments
- Subdomains form
- Subdomains come together to form a partly folded domain; a “molten globule” that can rearrange, (tertiary strucutre still partly disordered)
- Final domain strucutre emerges, small conformational adjustments to give final compact native structure
Stabilisation of protein folding
- 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
3 ways it can fold
- Chaperone-independent
- Chaperone-depended e.g Hsp70
- Chaperoning-dependent e.g GroEL-GroES
Unfolding proteins occurs if the non-covalent bonds break due to…
- change in pH
- heating (kinetic energy)
- more
If you change the side chains - not going to face the same properties - heat cause bonds to vibrate breaking hydrogen bonds
If you change the side chains - not going to face the same properties - heat cause bonds to vibrate breaking hydrogen bonds
Can protiens in living orgasnisms that are folded normally sometimes change their shape and become misfolded?
Yes
Some misfolded proteins can ______ other _____ to change their _____ as well, sometimes with ________ ___________
Some misfolded proteins can cause other proteins to change their shape as well, sometimes with disastrous consequences
How do prion diseases form
- prp changes its shape and form aggregates that cause Brian damage
Prion diseases include
- Bovine spongiform encephalopathy (BSE)
- Creutzfeldt-Jacob disease
- Kuru
What is a prion
- the protiens that cause the problem are called prions for “protiens infections agent”
The abnormal form of a prion protein induces the normal form of this protein to become misfolded
The abnormal form of a prion protien induces the normal form of this protien to become misfolded
What transformation does prion disease induce
A —-> B transformation
Treatment for prion diseases
- no treatment available
- always fatal
Model for prion conformation
Diseases which protein misfolding or aggregation is THOUGHT to contribute to
- alzheimers disease
- type two diabetes
- prions are not involved in these ailments
- abnormally folded protien called amyloid is thought to contribute
All the _____ required for a protein to ___ is in the ____ _____ of _____ _______
All the requires information requires for a protein to fold is in the primary sequence of amino acids
A domain is….
An independently folded region of a protien, often with a specific role, and usually with a hydrophobic core
The tertiary strucutre of a protein is largely stabilised by…
…non-covalent interactions
Protien misfiling can lead to..
Disease
