Polar- Tyrosine, tryptophan, asparagine, glutamine. cytesine, serine, theronine

nonpolar- glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine

Tyrosine, tryptophan and phenylalanine absorb and give uniques UV spectrums

it is the pH when ionisable groups spend 50% of time charged and 50% uncharged

it is protonated when pH is less than pH, since it is surrounded by protons

least soluble state since less water interaction and no repulsion of proteins

Motifs are pattens in the sequence linked with a particular function

typically a folded folded protein is 50KJ more stable than the unfolded

protein entropy decreases

unfolded protein has hydrophobic side chains facing water which is unfavourable

Refolding experiments revealed incorrect disulphide formation prevents correct structure

Levinthal paradox- assume each carbon can have one of three bond angles for 100 amino acids then th etime it takes for the formation of the correct structure is 1.6x10^27 years, so the searching process is not random

unfolded polypeptide undergoes folding via series of partially folded intermediates

after a few amino acids have been correctly established the rest forms

this is because of the energy landscape becoming more stable

It is the linear covalent arrangement of amino acid residues that compose it, linked by peptide binds

Oligopeptides are short chains of amino acids linked by peptide bonds and longer chains are refered to as polypeptides (200-500 residues)

Can be covalently modified by phosphorylation of glycosylation which can alter the mass of those residues

They are the particular combination of 2 or more secondary structures that form a 3D structure

some are stable after being isolated from the rest of the protein but others do not form thermodynamically stable structures in the absence of other portions of the protein

a helices from multiple separate polypeptide chains coil abouth one another

many fibrous proteins and transcriptional factors assemble into dimers or trimers by using this motif

They bind as each helix has an alipathic side chain strip that interact with a similar strip in the adjacent helix so sequestering hydrophobic groups away from water and stabilising the assembly of multiple independent helices; the hydrophobic strops along only one side because the primary structure of each helix is composed of heptad repeats (in which the side chains of first and fourth residues are alipathic and others are often hydrophilic)

this is a common calcium binding motif that contains 2 short a helices connected by a loop

Ca2+ ion binds to oxygen atoms in conserved residues in the loop when the concentration of Ca2+ in the cell is high enough, the binding can induce a conformational change in the protein

This bonds behaves somewhat like a planar double bond, the portions on either side of the peptide bond can be orientated in either trans or cis configuration relative to peptide bond

In the bond, the carbonyl carbon and amide nitrogen and atoms directly bonded to them all lie in fixed plane, little rotation about the peptode bond itself is possible

teh only flexibility in a polypeptide chain is the rotation of fixed planes of adjacent peptide bonds wiht respect to one another about the amino nitrogen bond and carbonal carbon bond

Cells use PPIases to catalyses cis/trans isomerisations so that Pro in folding protein forms the proper isomer, these isomerisations can drastically alter protein structure

The native state of any protein not intrinsically disordered, will adapt a very few closely related stably form conformations

the features of well ordered protein that limit conformations are side chain properties and polypeptide backbone sequence (e.h. Trp has large side chain so no tight packing, Arg has positive side charge so attract negative)

can be induced by thermal energy, pH extremes, denaturants (like urea, guanidine hydrochloride at 6-8M); and treatment with reducing agents (Like Beta mercaptoethanol) can further desabilse

Spontaneous unfolding occurs because increase in entropy that occurs because a denatured protein can adopt many non-native conformations (increased disorder)

However when a pure sample is placed back in normal conditions some denatured proteins can spontaneously refold like in Anfinsen's experiments

so the information contained in the primary structure is enough to direct correct folding

similar 3D structure of proteins with similar amino acid sequences

total cytosolic protein concentration can be 300mg/ml in mammalian, these high concentrations favour formation of aggregates by increasing chances a nascent protein will encounter proteins prior to folding and so aggregate into awter-insoluble mass due to hydrophobic effect

Intrinsically disordered proteins are less likely to form deleterious aggregates as have fewer hydrophobic side chains, whereas newly synthesised have high risk as not yet properly folded

95% of proteins in cells are in native control, without chaperones the cell would waste too much energy to destroy aggregates

chaperones facilitate folding by preventing aggregation yb binding to polypeptide or sequestering it from other partially unfolded proteins so nascent protein has time to correctly fold

They help fold newly made proteins or refold misfolded or unfolded proteins; sometimes the protein fails to fold so the chaperones re-engage for additional cycles

chaperones can disassemble potentially toxic protein aggregrates that form due to misfolding

They bind to client proteins and use a cycle of ATP binding, hydrolysis and exchange to induce conformational changes. ATP used for enhanced binding, switching own configuration, optimise folding and returning to initial state

They bind to a short segment of protein and stabilise unfolded/partially folded proteins and prevent aggregation and degradation

Bind to nascent cahin as being synthesised, as leaving ribosom

When an ATP is bound at nucleotide binding domain Hsp70 is in open conformation

co-chaperone accessory proteins (DnaJ/Hsp40) stimulate ATP hydroylsis (increase hydrolysis rate 100-1000 times the induces a large conformational change in substrate binding domain causing closed conformation, in which the substrate is tightly locked in

exchange of cytosolic ATP for bound ABP stimualted by otehr proteins (GrpE/BAG1) converts it back to open conformation, releasing the substrate and freeing it to continue folding

if the released substrate does not fold properly it can rebind to another chaperone and repeat

they have strong evolutionary conservation since similarity is 55%

They help cells fold partially folded client proteins and cope with denatured proteins from stress

they can form a relatively stable complex with a client until signal causes dissociation

unlike Hsp70, they function as a dimer in a cycle. Rapid ATP binding leads to conformational change in which nucleotide binding domains and substrate binding domains move together into a closed conformation

The closed conformation means the client protein may undergo folding, binding of clinets to Hsp90 occurs at different points

ATP hydrolysis causes change that may include highly compact form, client folding, client protein release adn additional folding of unbound client. ADP then released

these are huge cylindrical supramolecular assemblies with a centre of chambers in will protein enters; the chamber allows folding and is formed from 2 rings of olgiomers

composed of 2 rings each with 7 subunits and each ring is a folding chamber into which an unfolded protein enters

They have 8-9 homomeric or heteromeric subunits in each ring and lid funciton is incorporated into those subunits

a misfolded protein enters and the second chamber is then blocked by a GroES lid, each ring of 7 GroEL subunits binds 7 ARPs, hydrolyses them to set coordinated GroES and protein binding, folding and release

the polypeptide remains in chamber capped by lid adn undergoes folding until ATP hydrolysis induces binding of ATP na da differenct GroES to the ring

this binding causes GroES led and ADP to be released which opens the chamber and lets out folded protein

ATP binding and hydrolysis in presence of bound client protein leads to closing of the lid and folding of client in sequestered environment withing the folding chamner

release of Pi opens the lid adn release the substrate adn ADP