PHSC1212 Biochemistry - Lecture 6 Protein Structure pt 2

Allosteric effects

when a protein changes shape as another molecule (a modulator) binds to it

Modulator

a molecule that binds to a protein and changes its shape

Hemoglobin

an example of a protein that can bind 4 molecules and changes shape as each molecule binds

4 molecules of oxygen

What can hemoglobin bind?

Higher affinity for oxygen

What does hemoglobin have as each oxygen molecule binds to it?

Cooperative binding

an allosteric effect where the molecule's affinity for a ligand changes after the first ligand binds to one of its multiple binding sites

Disordered

another name for unfolded regions

Low amounts of hydrophobic residues

What causes unfolded or disordered regions in proteins?

Flexibility for more binding accessibility

What can unstructured regions of proteins allow for?

CREB

a disordered transcription factor example that searches out and binds to a transcription co-activator called CBP

CBP

transcription co-activator example that CREB binds to

CREB binding to CBP

transcription factor and transcription co-activator pair example that undergoes a disordered to ordered transition and folds into a pair of helices

Amino acid sequence, temperature, pH

What dictates the folding of a protein?

Hydrophobic

very important interactions in protein folding

Native state

a biologically active 3D structure of a folded protein

Low energy, biologically active 3D structure

What is the native state of a protein?

Released and more disordered

What happens to water molecules after folding due to not having to form ordered cages around hydrophobic groups?

Smaller

proteins that often require no intermediates

Larger

proteins that often go through intermediate states before rearranging into the final folded confirmation

Chaperones

proteins that aid in the folding of proteins, refolding partially unfolded proteins, and targeting of irreparable misfolded proteins to proteasomes

Protein folding, refolding partially unfolded proteins, and targeting irreparable misfolded proteins to proteasomes

What do chaperones aid in?

Irreparable misfolded proteins

What do chaperons target to proteasomes for?

Prevent inappropriate hydrophobic interactions

How do chaperones assist in protein folding?

Binding to hydrophobic regions

How do chaperones prevent inappropriate hydrophobic interactions?

Heat shock proteins

a family of proteins where many act as chaperones

During and after polypeptide synthesis

When do chaperones protect unfolded proteins?

Whether chaperone is bound to ATP or ADP

What does affinity for a chaperone molecule depend on?

Binds polypeptide

What does a chaperone molecule do to a polypeptide when bound to ADP?

Releases polypeptide

What does a chaperone molecule do to a polypeptide when bound to ATP?

Cytosol and ER

Where can chaperones assist protein folding?

Denaturation

the process of physical and chemical agents disrupting the folded structure of a protein

Secondary, tertiary, and quaternary

What protein structures does denaturation disrupt?

Primary

Which protein structure and its bonds are not disrupted by denaturation?

Usually permanent

How long does a denatured protein stay denatured?

Acids or bases, organic solvents, detergents, reducing agents, salt concentration, heavy metal ions, temperature changes, mechanical stress

What can cause denaturing of proteins?

Alters ionization states

How do acids and bases denature proteins?

Disrupt hydrophobic interactions

How do organic solvents and detergents denature proteins?

Break disulfide bonds

How do reducing agents denature proteins?

Salt ions interact with water

How does increased salt concentration denature proteins?

Can disrupt salt bridges and bind sulfhydryl groups

How do heavy metal ions denature proteins?

Lead and mercury

heavy metal ion examples

Causes molecular vibrations that disrupt hydrogen bonding

How do temperature changes, like increasing heat, denature a protein?

Disrupt hydrogen bonds

How does mechanical stress denature proteins?

Amphipathic

What type of molecules are detergents?

Fibrous

rod-like or sheet-like proteins

Long strands of alpha helices or beta pleated sheets

typically contained in fibrous proteins

Structural

What type of roles do fibrous proteins have?

Extracellular matrix proteins and intermediate filaments

fibrous protein examples

Collagen and elastin

examples of extracellular matrix proteins that are fibrous

Keratin

an intermediate filament fibrous protein example

Globular

more complex structure than fibrous proteins

Enzymes, receptors, transporters, signaling

globular protein examples