proteins - lecture 3

Dihydrofolate reductase

An enzyme that reduces dihydrofolate to tetrahydrofolate, reducing nucleotide synthesis and inhibiting cancer cell proliferation.

Myoglobin- structure

globular protein,153 amino acids, extremely compact, no symetry

Fibrous proteins

Proteins that use special helices to facilitate their length, such as keratin. Keratin consists of two right-handed alpha helices coiled around each other to form a left-handed superhelix called an alpha helical coiled coil, creating a stable structure.

Collagen

The most abundant protein in mammals, consisting of three helical polypeptide chains with glycine every third amino acid. It forms a superhelical cable stabilized by hydrogen bonds between strands, with a crowded interior that can only accommodate glycine.

Protein folding and function

Protein folding is an all-or-nothing process that maintains partially correct intermediates. Predicting protein folding from amino acid sequence is almost impossible. Chaperone proteins assist in the folding process, preventing misfolding and aggregation.

Energy considerations

Protein folding is energetically favorable, with the folded state associated with lower free energy compared to the unfolded state. Denaturation disrupts a protein's native structure, while renaturation restores the native structure.

Protein folding process

The process begins with the linear sequence of amino acids (primary structure), followed by the formation of secondary structures (alpha helices and beta sheets) through hydrogen bonding. Interactions between amino acid side chains lead to the three-dimensional tertiary structure. Quaternary structure arises when multiple polypeptide chains associate.

Cellular locations of protein folding

Proteins fold in the cytosol, endoplasmic reticulum (ER), mitochondria, chloroplasts, and Golgi apparatus, depending on their destination and function.

How a protein folds properly

Proper protein folding requires the addition of a chemical denaturant (e.g., urea) and a reducing agent (e.g., beta-mercaptoethanol) for unfolding, followed by refolding in the absence of denaturants and reducing agents.

Disease and proteins

Misfolded or incorrect proteins can cause diseases such as Parkinson's and neurological diseases. Protein folding serves as quality control, preventing the deposition of misfolded proteins.

Thermodynamics of protein folding

Protein folding involves a hydrophilic collapse, where the protein folds to minimize exposure of hydrophobic residues to water.

what is the inside of myoglobin mostly made of

non polar residues

how do fibrous proteins faciltate their length

special helixes

the formation of keratin

two right handed alpha helixes coiled into a left handed superhelix

structure of collagen

three helical polypeptide chains, glycine every 3rd, no hydorgen bonds within the structure, three strands bond by hydrogen

Chaperone Proteins

• Molecular chaperones assist in the folding process, ensuring that proteins reach their functional conformation.

• Chaperones prevent misfolding and aggregation and can facilitate correct folding pathways.

why is protein folding energetically favorable

folded state is often associated with lower free energy compared to the unfolded state

which organelle does protein folding occur in

cytosol endoplasmic reticulum and mitochondria or choloplasts finish their own folding

what is needed for a protein to fold properly

• Unfolding of ribonulcease A

• Addition of a chemical denaturant - urea 

• Reducing agent  beta -Mercaptoethanol) 

• Refolding of RnaseA