Proteins

Proteins? What is its How does it How is its How does it How is it Where is it What are its

H2NH2N R1 O O H C C N H H C R2 C O OH H H O H H H2NH2N R1 O C C N H C R2 C O OH H H

Peptide bond formation Condensation reaction forms a peptide bond. 

The peptide bond

Peptide

The planar peptide bond Three bonds separate sequential  carbons in a polypeptide chain. The N—C  and C  —C bonds can rotate, described by dihedral angles designated  and , respectively. The C—N peptide bond is not free to rotate.

Rotation around the peptide bond is not permitted Rotation around bonds connected to the alpha carbon is permitted  (phi): angle around the  -carbon—amide nitrogen bond  (psi): angle around the  -carbon—carbonyl carbon bond In a fully extended polypeptide, both  and  are 180°

Steric Hindrance While many angles of rotation are possible, only a few are energetically favorable

Ramchandran plot

Some f and y combinations are very unfavorable because of steric crowding of backbone atoms with other atoms in the backbone or side-chains Some f and y combinations are more favorable because of chance to form favorable H-bonding interactions along the backbone Ramachandran plot shows the distribution of f and y dihedral angles that are found in a protein shows the common secondary structure elements reveals regions with unusual backbone structure While many angles of rotation are possible only a few are energetically favorable

Rotation

Alpha helix

The backbone is more compact with the  dihedral (N–C  —C–N) in the range ( 0° <  < -70°) Helical backbone is held together by hydrogen bonds between the nearby backbone amides Right-handed helix with 3.6 residues (5.4 Å) per turn Peptide bonds are aligned roughly parallel with the helical axis Side chains point out and are roughlyperpendicular with the helical axis

Left and right handedness

Not all polypeptide sequences adopt a helical structures Small hydrophobic residues such as Ala and Leu are strong helix formers Pro acts as a helix breaker because the rotation around the N-Ca bond is impossible Gly acts as a helix breaker because the tiny R group supports other conformations

Peptide dipole

The backbone is more extended with the  dihedral (N–C  —C–N) in the range ( 90° <  < 180°) The planarity of the peptide bond and tetrahedral geometry of the  -carbon create a pleated sheetlike structure Sheet-like arrangement of backbone is held together by hydrogen bonds between the more distal backbone amides Side chains protrude from the sheet alternating in up and down direction Parallel or antiparallel orientation of two chains within a sheet are possible In parallel  sheets the H-bonded strands run in the same direction In antiparallel  sheets the H-bonded strands run in opposite directions Beta strand is an extended structure… 3.5 A between R groups in sheet compared to 1.5 in alpha helix Beta Sheet

Anti ‐ parallel B sheet R ‐ groups spaced at 3.5 A Distance R groups alternate above and below plane of sheet Parallel B sheet R ‐ groups spaced at 3.25 A distance R groups alternate above and below plane of sheet Parallel and antiparallel

 -turns occur frequently whenever strands in  sheets change the direction The 180° turn is accomplished over four amino acids The turn is stabilized by a hydrogen bond from a carbonyl oxygen to amide proton three residues down the sequence Proline in position 2 or glycine in position 3 are common in  -turns The Beta turn

Cis and Trans proline

Tertiary Structures Tertiary structure refers to the overall spatial arrangement of atoms in a polypeptide chain or in a protein One can distinguish two major classes – fibrous proteins typically insoluble; made from a single secondary structure – globular proteins water-soluble globular proteins lipid-soluble membrane proteins

Fibrous Proteins

Keratin

Hair

Collagen

Silk

Globular Proteins

Myoglobin Tertiary

A simple motif

An elaborate motif

X-ray diffraction

NMR (1D)

NMR (2D)

Constructing large motifs

Quaternary structure Quaternary structure is formed by spontaneous assembly of individual polypeptides into a larger functional cluster Oligomeric Subunits are arranged in Symmetric Patterns

Hemoglobin

Rotational symmetry

Dihedral symmetry

Protein Denaturation

Protein Renaturation

Protein folding

Folding pathway

Molten globules

Chaperones