Orders of protein structure and protein folding and denaturation

four levels of protein structure

primary, secondary, tertiary, and quaternary

simplest level of protein structure

primary structure, simple sequence of amino acids in a polypeptide chain

primary structure has

its own set of amino acids assembled in a particular order

the sequence of protein in a primary structure is determined by the

DNA of the gene that encodes the protein, a change in the gene’s DNA sequence may lead to a change in the amino acid sequence of the protein and can affect the protein’s overall structure and function

the second level of protein structure is

secondary structure

secondary structure refers to

local folded structures that form within a polypeptide due to interactions between atoms of the backbone (backbone refers to the polypeptide chain apart from the R group)

secondary structure does not involve

R group atoms

the most common types of secondary structures are the

alpha helix and the beta pleated sheet

alpha helix and beta pleated sheet in the secondary structures are held in shape by

hydrogen bonds, which form between the carbonyl of one amino acid and the amino H of another

in an alpha helix, the carbonyl (C=O) of one amino acid is hydrogen bonded to the amino H (N-H) of an amino acid that is

four down the chain

the carbonyl of amino acid 1 forms a hydrogen bond to the N-H of amino acid 5 pattern of bonding

pulls the polypeptide chain into a helical structure with each turn of the helix containing 3.6 amino acids - the R groups of the amino acids stick outward from the alpha helix, where they are free to interact

in a beta pleated sheet,

two or more segments of a polypeptide chain line up next to each other, forming a sheet like structure held together by hydrogen bonds.

In Beta pleated sheets, the hydrogen bonds form between

carbonyl and amino groups of backbone, while the R groups extend above and below the plane of the sheet

the strands of a beta pleated sheet may be

parallel or antiparallel

parallel in beta pleated sheets point

in the same direction meaning that their N- and C-termini match up

antiparallel in beta pleated sheets point

in opposite directions meaning that their N-terminus of one strand is positioned next to the C-terminus of the other

proline is sometimes called a

“helix breaker” because its unusual R group creates. abend in the chain and is not compatible with helix formation

tryptophan, tyrosine, and phenylalanine are often found in

beta pleated sheets perhaps because the beta pleated sheet structure provides plenty of space for the side chains

tertiary structure -

the overall three-dimensional structure of a polypeptide

the tertiary structure is primary due to

interactions between the R groups of the amino acids that make up the protein

R group interactions that contribute to tertiary structure include

hydrogen bonding, ionic bonding, dipole-dipole interactions, and london dispersion forces

An interaction that is important to tertiary strcurre are

hydrophobic interactions, in which amino acids with nonpolar, hydrophobic R groups cluster together on the inside of the protein, leaving hydrophilic amino acids on the outside to interact with surrounding water molecules

disulfide bonds are found in

tertiary structures `

disulfide bonds -

covalent linkages between the sulfur-containing side chains of cysteines, are much stronger than the other types of bonds that contribute to tertiary structures

quaternary structure

proteins made up of multiple polypeptide chains (subunits), the subunits come together to make quaternary structure

interactions that hold the subunits of quaternary structure together are

weak interactions such as hydrogen bonding and london dispersion forces

denatured proteins are usually

non-functional

denaturation can be

reversed

since the primary structure of the polypeptide is still intact (the amino acids haven’t split up), it may be able to

refold into its functional forma if its returned to its normal environment

chaperone proteins assist in

folding amino sequences

hydrophobic effect

non-polar amino acids cluster together to avoid water, releasing water molecules into the surrounding environment and increasing the systems entropy

hydrophobic effect is

the main driver of protein folding, ensuring that the proteins achieve their functional forms

hydrogen bonds forming between side chains to

stabilize the structure

ionic bonds aka salt bridges act as

powerful attractions between positively and negatively charged side chains, adding strength to the proteins framework

disulfide bonds provide

extra reinforcement, locking parts of the protein together with strong covalent links

Van Der Waals forces help

fine-tune and stabilize the overall shape

hydrophobic interactions driving force behind this effect is

entropy: as hydrophobic residues aggregate, water molecules are released from their structured arrangements around these residues, increasing the entropy of the system

hydrogen bonds form between

polar side chains and contribute significantly to the proteins stability, can occur between side chains and the backbone, or between side chains themselves

ionic bonds (salt bridges) form between

positively charged (basic) and negatively charged (acidic) side chains - ionic bonds are strong and contribute to the overall stability of the protein structure

disulfide bonds are

covalent bonds that form between the sulfur atoms of two cysteine residues, provide significant stabilization particularly in extracellular proteins

Van Der Waals force occur between

all atoms that are in close proximity, they help fine-tune protein structure and stability

entropic contributions to folding - protein folding is driven by a balance. of

enthalpic and entropic changes

enthalpic and entropic changes are

conformational entropy and solvent entropy

conformational entropy:

as a protein folds, it adopts a more ordered structure, which decreases its conformational entropy, this loss is offset by other entropic gains

solvent entropy:

the hydrophobic effect plays. a critical role, when the hydrophobic side chains cluster together in the interior of the protein, water molecules that are structured around these hydrophobic residues are released into the bulk solvent, this release increases the entropy of the surrounding water molecules, which is the driving force of the folding process

forces stabilizing quaternary interactions

hydrophobic interactions, hydrogen bonds, ionic bonds, disulfide bonds

quaternary structures - hydrophobic interactions

subunits often interface through hydrophobic regions to minimize exposure to the aqueous environment, driven by entropy

quaternary structures - hydrogen bonds

stabilize the interfaces between subunits

quaternary structures - ionic bonds

can form between charged residues at the interfaces of subunits

quaternary structures - disulfide bonds

in some multi-subunit proteins, disulfide bonds can link different polypeptide chains

the process of folding is guided by the protein’s primary sequence but is often assisted by

molecular chaperones

chaperones, including …, play crucial roles in

heat shock proteins ( HSPs) and chaperonins, ensuring correct protein folding

chaperone proteins are needed to assist

protein folding because the cellular environment can be crowded and stressful, which can cause nascent or misfolded proteins to aggregate or fold incorrectly

chaperones help by

stabilizing proteins, preventing aggregation, and providing optimal environment for proper folding, ensuring that proteins achieve their correct functional conformations

molecular chaperones: proteins bind to nascent or partially folded polypeptides precenting

improper interactions that can lead to aggregation or misfolding - HSP70 chaperones bind to hydrophobic regions of nascent proteins

chaperonins are

large cylindrical complexes that provide a protected environment for protein folding - a well known example is the GroEl/GroES system in bacteria

GroEl/GroES

GroEL is a barrel-shaped protein that encapsulates. thepolypeptide, while GroES acts. asa cap, this isolation prevents aggregation and allows the protein to fold properly within the chamber

denaturation is a process that

alters a proteins native conformation, typically due to changes in environmental conditions such as temperature, pH, or chemical exposure.

denaturation affects the proteins

secondary, tertiary, or quaternary structure, but not its primary sequence

elevated temperatures increase the

kinetic energy of molecules, disrupting the non-covalent interactions that maintain the protein’s structure.

heat can cause the

unfolding of proteins, exposing hydrophobic residues that normally reside in the proteins interior

variation in pH can

alter the charge states of amino acid side chains; particularly those with acidic or basic groups

the changes in ph can disrupt

ionic bonds and hydrogen bonds that are critical for maintaining the proteins structure

certain chemicals such as urea and guanidine hydrochloride can

disrupt hydrogen bonding and hydrophobic interactions, leading to protein denaturation

denaturation can be

reversible and irreversible

reversible denaturation occurs when

the protein can refold into its native structure upon the removal of the denaturing agent, allowing it to regain its functionality

irreversible denaturation results in

a permanent loss of protein structure and function, often due to covalent modifications or aggregation of denatured proteins