3.2 | Protein Structures

Primary Protein Structure

sequence of an amino acid chain

Secondary Protein Structure

local folding of the polypeptide chain into helices or sheets

Tertiary Protein Structure

three-dimensional folding pattern of a protein due to side chain interactions

Quaternary Protein Structure

protein consisting of more than one amino acid chain

________ → ________ → ________ → ________

Amino Acid Sequence → Protein Structure → Protein shape → Protein Function

Primary Structure of Proteins

- AAs are linked together in a protein through peptide bonds
- distinctive of a protein (or polypeptide)
- tells its AA composition
⭐ protein's shape and function

1º Structure: protein's shape and function

dictated by the DNA base sequence in the gene

Each protein has its own _

Each protein has its own unique AA sequence

unique AA sequence

number, kind, order of attachment

[DYK] Frederick Sanger

(1953) sequenced/determined the 1º structure of insulin

Protein Backbone

- made by the linkage of each AA
- R groups are left outside the backbone

Insulin

- has 51 AA residues in its structure
- divided into 2 chains: Chain A & B

Insulin: 1º Structure

alike in several species but identical since there are residues that are different

(identical ba????)

Insulin in Humans

Chain A: T-S-I
Chain B: T

Insulin in Pig (Porcine)

Chain A: T-S-I
Chain B: A

Insulin in Cow (Bovine)

Chain A: A-S-V
Chain B: A

1º Structure: Peptide linkages

- planar
- 6 atoms lie in the same plane (C=O, C-N and N-H)

1º Structure: Planar Peptide Linkage Structure

- rigid
- rotation of C-N group is hindered
- cis-trans isomerism is possible: trans is highly favored

1º Structure: Effect

peptide bond planarity
- leads to zigzag arrangement of protein backbone

Post-1º Structure

- polypeptide starts to fold
- 1º AA structure contains all information necessary for folding the peptide chain into its "native conformation"
- leads to 2º structu

Secondary Structure of Proteins

- ordered 3D arrangements/regular folding in localized regions of a polypeptide chain
- AA acids are near each other

2º Structure: Arrangement

spatial arrangement

2º Structure: Binding force

H-bond between the amide (-NH) proton and carbonyl O (C=O).

2º Structure is dictated by _

2º Structure is dictated by 1˚ structure based on the AAs present

2º Structure: Types (2)

1. Alpha Helix
2. Beta-pleated Sheets

Alpha Helix

- single protein chain resembling coiled spring
- H-bonds between every fourth AA

Alpha Helix: Binding Force

results from intramolecular H-bonding between AA

Alpha Helix: R Group

stay outside the helix
- not enough space inside the helix

Alpha Helix: Helix

tightly wound that the space in the center is too small for solvent molecules to enter

Alpha Helix must _ to coil

Alpha Helix must have the same conformations (all D or all L) to coil

Beta-pleated Sheets

- "pleated" or zigzag pattern
- completed extended protein chain segments

Beta-pleated Sheets: Binding force

intermolecular or intramolecular H-bonds
- between 2 side-by-side chains or a single chain that is folded back on itself

Beta-pleated Sheets: R or side chains

below or above the sheet

Beta-pleated Sheets: Backbone

alternating top and bottom position

Beta-pleated Sheets: most frequently encountered structure

U-turn structure

Beta-pleated Sheets: Intermolecular H-bonding Directions (2)

1. Parallel
2. Antiparallel

Parallel H-Bonding

chains run in the same direction

Antiparallel H-Bonding

- chains run in opposite direction
- more stable because of fully collinear H-bonds

A protein structure that is neither a helix or beta-pleated sheet

Unstructured segments

Unstructured Segments

- structure that is neither a alpha helix or beta-pleated sheet
- flexibility: to interact with different substances

Tertiary Structure of Proteins

- overall 3D shape of a protein that defines the function of the protein
- interactions between AA side chains (R groups) that are widely separated from each other

3º Structure: Shape

fibrous or globular

(3 looks like 2 semi-circles = globular)

3º Structure: Interactions (4)

1. Disulfide Bonds
2. Electrostatic interactions
3. H-bonding
4. Hydrophobic interactions

(DEHH nag-iinteract kasi pabilog = globular siya)

Disulfide Bonds

- covalent bonds between Cys groups (-SH)
- strongest of the 3º interacting forces
- chains twist & bend

Electrostatic interactions

- aka salt bridges
- between acidic R groups and basic R groups

H-Bonding

- between polar, acidic and/or basic R groups
- -OH, -NH2,-COOH, -CONH2
- weak and easily disrupted by changes in pH and Temperature

Hydrophobic attractions

- between non-polar R groups
- orienting inwards avoiding common polar solvents
- momentary interactions brought by weak forces (London dispersion) that is common with alkyl-aryl R groups

*Hydrophilic Interactions

between polar or ionized groups + water on the surface of tertiary structure

Quarternary Structure of Proteins

- highest level of protein organization that only exists in a multimeric protein (with 2 or more polypeptide chains or subunits)
- 3D protein shape with 2+ independent peptide chains which result from noncovalent interactions between R groups

4º Structure in changing conditions

easily broken down

4º Structure in optimum conditions

restored

4º Structure: Subunits

- independent of each other; not covalently bonded
- usually contains an even number of subunits

4º Structure is produced by what interactions (3)

1. Electrostatic interactions
2. H-bond
3. Hydrophobic interactions