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
 Fibrous (structural) proteins
Keratin
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.
  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
protein
Left-handed coil coiled-coil
310 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 residue
3.6

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 low
Perms 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, stretchy
Several 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

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

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

N CH N CH
1 2 1 2
3CH2 H
H 3C 5 H 3C 5 3C
4 4 OH
C C
OH
H H H
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 repeat

100 - 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 24C

instead of 39 to form gelatin.

Scurvy-skin lesions, broken blood vessels, wounds don’t

heal, teeth fall out, one cannot stand.