Levels of Protein Structure - Primary (1°):

What is it?

What bonds are involved?

What does it determine?

-The amino acid sequence

-Held together by covalent peptide bonds

-Determines how the polypeptide backbone folds (3D protein shape)

Levels of Protein Structure - Secondary (2°):

What is it?

What bonds are involved?

What does it determine?

-Local regions of the peptide chain with common, repeating regions that fold in specific ways

-Non-covalent bonds (hydrophobic effects, Van-der-Waals, electrostatics, and hydrogen bonding)

-Determines if there is an alpha helix, beta sheet, or beta bend (among others)

Levels of Protein Structure - Tertiary (3°):

What is it?

What bonds are involved?

-The entire peptide chain/a single subunit and all its folding

-Non-covalent bonds (hydrophobic effects, Van-der-Waals, electrostatics, and hydrogen bonding)

Levels of Protein Structure - Quaternary (4°):

What is it?

What bonds are involved?

What does it determine?

-Complex of more than one peptide chain/subunit interacting

-Non-covalent bonds (hydrophobic effects, Van-der-Waals, electrostatics, and hydrogen bonding)

-Protein function, allostery

Secondary Structure - α Helices:

-Structure

-Common amino acids

-Bonds

-Charge

-Hydrophilicity

-R groups face outward, backbone faces inward and makes a right hand helix

-Leu (K), Glu (E), *Ala (A)* (Gly and Pro rarely/never seen)

-Hydrogen bonding between carboxyl and amino of the same strand, 4 residues apart, but each amino acid is close together

-α helices have an overall dipole moment (partial positive N-terminus, partial negative C-terminus)

-Can have a hydrophilic and hydrophobic side if hydrophobic amino acids occur every 3 or 4 residues

Secondary Structure - β Sheets:

-Structure

-Common amino acids

-Bonds

-Interactions between amino acids from the same strand with R-groups sticking up/down and sharp Pro/Gly β turn

-Val (V), Tyr (Y), Ile (I)

-Hydrogen bonding between (N) amino and (C) carboxylic group, each amino acid being far apart compared to α helices

Secondary Structure - β Turns:

-Structure

-Common amino acids

-Bonds

-Hydrophilicity

-4 amino acids where a sharp turn to a β sheet occurs

-Pro (P), Asn (N), Gly (G) (usually the 2nd or 3rd)

-Hydrogen bonding between oxygen (1^st residue) and amino group hydrogen (4^th residue)

-Mostly hydrophobic (Gly and Pro)

Motif:

What is it?

Example?

-Supersecondary structure, common combinations of secondary structure

-TIM barrel fold, alternative alpha helix and beta sheet folding

Domain:

What is it?

Example?

-Specific globular units in the protein that are independently stable and have a distinct function

-An α and/or β domain

Amino Acid:

How does moving an amino acid's functional group to the interior/exterior of the protein affect its pKa?

Interior: non-polar, hydrophobic

Neutral form favored as the charged form is energetically costly

-For acidic AA's (E, D, C, Y) pKa increases as group wants to keep its proton and avoid negative charge

-For basic AA's (K, R, H) pKa decreases as it wants to deprotonate and avoid positive charge

Exterior: polar, hydrophilic

Charged form is favored because of potential H-bonding with water

-For acidic AA's pKa decreases as the group wants to be deprotonated and have negative charge

-For basic AA's pKa increases is the group wants to be protonated and have a positive charge

Globular Protein Structure:

-Shape/structure

-Solubility

-Role

-Tertiary structure, small, compact and ball like

-Soluble in water

-Diverse in shape, size, and role

Fibrous Protein Structure:

-Shape/structure

-Solubility

-Role

-Types

-No tertiary structure, long parallel polypeptide chains w/ intervals of cross-linkage creating long fibers/sheets

-Mostly insoluble

-Structural role: Collagen, α keratin, fibroin

-Collagen: Gly every 3^rd AA, coiled tight and rigid

-α Keratin: all α helices, hydrophobic AA's, and stretchy

-Fibroin: β sheets, mostly Ala and Gly, many weak non-covalent bonds, smooth and flexible

Fibrous Protein Structure:

What gives it its strength/flexibility?

-Keratin gets its strength from cross-linking from covalent disulfide bonds between cysteine functional groups

-Fibroin is strong because many AA's can be packed in layered β sheets and flexible because the sheets can shift by each other

-Collagen is strong because of the tight coiling of helices and cross linkage

Amino Acid H-Bonding:

What parts of AA's donate/accept?

Polypeptide backbone:

amide hydrogen → donor

carbonyl oxygen → acceptor

Amino Acid H-Bonding:

Which AA R-groups both donate and accept?

-OH of S, T, and Y

-NH2 of N and Q

-Imidazole ring of H

Amino Acid H-Bonding:

Which AA R-groups accept?

Amino Acid H-Bonding:

Which AA R-groups donate?

-Amines/ammonium of K and R (basic)

-Indole ring of W