Protein Structure

Lecture 2/26/2003

Protein Structures

A study in the structure-function of proteins.

Amino acid sequence dictates function.

Structures are not “static” but breath and vibrate

Protein dynamics (movement) can be linked to function

Globular proteins = enzymes and catalysts

Fibrous proteins = structural or connective role.

Structure - function relationships

Some residues and chains are just disordered “Floppy” flexible which maybe required for function

Nails, hair, horns and feathers or forms

30 variants, tissue specific type I and type II

acidic negative charge basic positive charge

keratin - • hair- 20 M diameter• macrofibril 2000 Å parallel to hair • microfibril 80 Å and high sulfur cement protein.

Fibrous (structural) proteins Keratin

keratin proteins are helical but spacing differs from an helix

a 5.1 Å vs. 5.4 Å pitch. This change in pitch forms closely associated pairs of helices. Each pair consists of a type I and type II proteinLeft-handed coil coiled-coil310 AA residues 7-residue pseudo repeat.Helical wheel - Look down an helix and residues stick out from center of helix 3.6 residues/turn 360 = 100 per residue3.6

a - b - c - d - e - f - g a repeat on side of helix

Helical wheel diagram

a and d residues are nonpolar.

Protofilaments antiparallel strands

a - d are non-polar and face the same side of helix. 3.6 residues/turn

3.5 residues hydrophobic repeat

The hydrophobic strip aligns between two helices with 18 inclination from one to another.

They fit well together

Dimer protofilament microfibril macrofibril hair

keratin rich in cys and forms disulfides hard keratin cys content is high soft keratin cys content is cyst lowPerms reduce R-S---S-R bonds to 2R-SH Curly hair has more Cys residues.

Protein helices are stretchy and can elongate

When keratin is stretched it can form a more sheet like structure.

keratin of feathers and nails are extended and have a more rigid and stiff consistency

epidermolysis bullosa simplex and epidermolytic hyperkeratosis are keratin related diseases involved in the loss of mechanical integrity of the shin.

Silk Fibroin a pleated sheet

From spider and insect webs, cocoons, nests and egg sacks.An almost fully extended sheet that cannot stretch and is

strong.

This is why spiderman can support his weight on the web material!!

Fibroin and sericin = web

sericin is an amorphous gummy protein

Adult moths dissolve (hydrolyze) their cocoons by cocoonase, this digests sericin, clothmoths do the same.

Boiling water also removes sericin and leaves fibroin or silk.

Extended parallel sheets of (-Gly-Ser-Gly-Ala-Gly-Ala-)N

Ala from one sheet interdigitates with Ala from another sheet

Silks from different species have different interdigitating groups and have differing physical properties.

Silk fibers are strong when extended but cannot be stretched because of the fully extended sheet form of fibroin

Collagen - Triple helical cable

Bones, teeth, cartilage, tendon, ligament, blood vessels and skin matrix

Strong, flexible, stretchySeveral types

I [1 (I)]2 2I skin, bone tendon, cornea vessels

II 1 (II)3 cartilage

III [1 (III)]3 vessels, fetal skin

Type I 285 kDA 14A wide

3000 A long 30 distinct peptide types 16 variants

1/3 Gly 15-30% -4-Hydroxyproline (Hyp) some 5-Hydroxylysyl (Hyl)

4-Hydroxyprolyl 3-Hydroxyproylyl(4-Hyp) (3-Hyp)

C

CH2H3C

N CH

C

CH3C

N CH12 21

3 3OH

C C

H

4 4

OH H H H

5 5

Gly-X-Y X often Pro Y often Hyp like a poly Gly or poly Pro helix

Left-handed 3.0 residues/turn pitch 9.4 extended conformation the prolines avoid each other.

3 left handed helices combine in a triple rt handed coil.

Rope twist or metal cable longitudinal force (pulling) is supported by lateral compression opposite twisted strands prevents twists from pulling out.

Collagen helices are organized into fibrils.

689 A hole repeat100 - 2000 A diameter different types make different arrays dark us light areas on fibril

Hydrophobic repulsion drives fibril formation possible Van der Waals attraction due to packing.

Collagen is 0.4 12% carbohydrate (linked sugars)

Vitamin C is required for hydroxyproline formation

Hydroxyproline gives collagen stability and strength by H-bonding.

Without prolyl hydroxylase collagen denatures at 24C instead of 39 to form gelatin.

Scurvy-skin lesions, broken blood vessels, wounds don’t heal, teeth fall out, one cannot stand.