Protein Structure

1
Protein Structure

• Lecture 2/26/2003

2
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

3
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
4
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.

5
(No Transcript)
6
? keratin proteins are helical but spacing
differs from an a 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 ? ? ?
7
(No Transcript)
8
Helical wheel diagram a and d residues are
nonpolar.
Protofilaments antiparallel strands
9
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.
10
Protein helices are stretchy and can
elongate When keratin is stretched it can form a
more sheet like structure. b-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.
11
Silk Fibroin a b 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.
12
Extended parallel ? sheets of (-Gly-Ser-Gly-Ala-Gl
y-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.
13
Silk fibers are strong when extended but cannot
be stretched because of the fully extended sheet
form of fibroin
14
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 3000 A long 30 distinct peptide types 16
variants
15
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
2
1
1
2
H
CH2
3
H3C
C
3
5
5
H3C
OH
4
4
C
C
OH
H
H
H
16
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.
17
(No Transcript)
18
Rope twist or metal cable longitudinal force
(pulling) is supported by lateral compression
opposite twisted strands prevents twists from
pulling out.
19
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)
20
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 dont heal,
teeth fall out, one cannot stand.