Chapter 4- 3D Structure of Proteins

Stucture of Proteins

Unlike most organic polymers protein molecules adopt a specific 3D conformation (Native fold)

Structure = Biological Function

Entropy Cost

Peptide Bonds

Structure of protein is partially dictated by the properties of the peptide bond

Resonance causes the Peptide bonds to:

• be less reactive compared with esters for example

• To be rgid and nearly planar

• To exhibit a large dipole moment in favor of trans configuration
  
  

Secondary Structure

Alpha Helix

• Stabilized by hydrogen bonds between nearby residues

Beta Sheets

• stabilized by hydrogen bonds between adjacent segments that may not be nearby

Irregularr arrangement of the polypeptide chain is called the random coil (loops)

Alpha Helix

Helical backbone is held together by hydrogen bonds between the backbone acids of amino acids 4 away

Is a right-handed helix with 3.6 residues per turn- Right hand is more energenically favorable

peptide bonds are aligned roughlly parallel with the helical axis

side chains point out and are roughly perpendicular wiht the helical axis

Carboxyl groups point down and amino groups point up in the structure (Causes a partial positive charge at the top and negative at the bottom)

Helix Stability

not all polypeptide sequences adopt helical structures

Small hydrophobic residues such as alanine and leucine are strong helix formers

Proline acts as a helix breaker because the rotation areound the N-Ca bond is impossible

Glycine acts as a helix breaker because the tiny R group supposts other configurations

Helix Dipole

All peptide bnds in the helix have a similar orientation

the helix has a large macroscopic dipole moment that is enhanced by unpaired amides and carbonyls near the ends of the helix

negativley residues often occure near the end of the helix dipole

Idea: Top of helix has partial positive charge and bottom has a partial negative charge

Beta Sheets

Pleated sheet like structure

Sheet like arrangement of the backbone is held together by the hydrogen bonds between the backbone amids in different strands

Side chains protude from the sheet alterating in an up and down direction

Parallel Beta Sheets

In parallel beta chets the H-bonded strands run in the same direction- this makes the hydrogen bonds bent and weaker

Antiparallel Beta Sheets

In antiparallel beta sheets, the H-bonded strands run in opposite directions- resulting in linear and stronger hydrogen bonds

Beta Turns

beta turns occur frequently whever strands in the beta sheets change the direction

the 180 turn is accomplished over four amino acids

the turn is stabilized by a hydrogen bond form a carbonyl oxygen to amide roton three residues down the sequence

Proline in position 2 or glycine in position 3 are common in beta turns

Proline Isomers

Most peptide bonds not involving proline are in the trans configurations (99%)

for peptide bonds involving proline about 6% are in the cis configuration and mots of those include B turns

Proline is catylazed by proline isomerase

Tertiary Structure

Tertiary structure refers to the overall spatial arrangment of atoms in a protein

Stabilized by numerous weak interations between amino acid side chains

• largely hydrophobic and polar interactions

• can be stabilized by disulfide bonds

interacting amino acids are not neccessarily next to each other in the primary sequence

Two Major Classes: Fibrous and Globular

Quaternary Structure

The assembly of individual polypeptides into larger functional clusters

Motifs (Folds)

Specific arrangement of several secondary structure elements- can be all helixes/sheets/both

Recurring structures in numerous proteins

Globular proteins are composed of different motifs folded together