Proteins

Proteins?

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

H2N

R1

O

O

H

C

C

N

H

H

C

R2

C

O

OH

HH

O

H

H

H2N

R1

O

C

C

N

H

C

R2

C

O

OH

HH

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°

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Steric Hindrance

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

Ramchandran plot

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• Some f and y combinations are very unfavorable because of steric crowding ofbackbone atoms with other atoms in the backbone or side-chains• Some f and y combinations are more favorable because of chance to formfavorable H-bonding interactions along the backbone• Ramachandran plot shows the distribution of f and y dihedral angles thatare 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

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• 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 directionsBeta strand is an extended structure… 3.5 A between R groups in sheetcompared to 1.5 in alpha helix

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Beta Sheet

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Anti‐parallel B sheetR‐groups spaced at 3.5 ADistanceR groups alternate aboveand below plane of sheet

Parallel B sheetR‐groups spaced at 3.25 AdistanceR groups alternate above andbelow 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

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 proteinstypically insoluble; made from a single secondary structure– globular proteins water-soluble globular proteins lipid-soluble membrane proteins

Fibrous Proteins

Keratin

Hair

Collagen

Collagen

Silk

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 assemblyof individual polypeptides into a larger functional cluster

• Oligomeric Subunits are arranged in Symmetric Patterns

Hemoglobin

Rotational symmetry

Dihedral symmetry

Protein Denaturation

Protein Denaturation

Protein Renaturation

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Protein folding

Folding pathway

Molten globules

Chaperones