Transcript Polypeptide and protein structure

Structure-Function relationship
Nafith Abu Tarboush
DDS, MSc, PhD
[email protected]
www.facebook.com/natarboush
The heme
Myoglobin
 The first to be
determined structurally
 A single polypeptide
chain (153 a.a)
 A single heme in a
hydrophobic pocket
 8 -helices; no -sheets
 Most polar (exterior)
 Nonpolar (interior)
 Two His residues
 Fe(II) coordination
Hemoglobin
• A tetramer 22: -chains
(141 a.a) & -chains (146 a.a)
• 1 heme group in each (4O2)
• Myoglobin (storage) vs.
hemoglobin (transport):
positive cooperativity &
saturation percentage
• lungs (100 torr), capillaries
(20 torr)
Conformational Changes Accompany Hb Function
 Oxygenated vs. deoxygenated (different crystal structures)
 Bohr effect: (tissues vs. lungs): lower pH → ↑H+→ protonation (ex. His146) →
Asp94- His146 salt bridge → lower O2 affinity
 Oxy form is a stronger acid (less H+ affinity) than de-oxy (higher H+ affinity)
 CO2 (tissues vs. lungs) → H2CO3 → HCO-3+H+ → ↓ pH (less O2 affinity)
 O2 binding affinity, CO2 & H+ in
myoglobin
Conformational Changes Accompany Hb Function
 2,3 BPG have an allosteric binding, lower affinity
 Hb F has a higher affinity for O2 due to:
 α2γ2
 Less affinity to BPG (adult hemoglobin, βHis143-BPG
salt bridge, fetal hemoglobin, the γ –Ser instead of His)
The Collagen Triple Helix
 The most abundant protein in vertebrates
 Organized in water-insoluble fibers
 Have a great strength
 Consists of three polypeptide chains
wrapped around each other in a ropelike
twist, or triple helix
 Has a repeating sequence of the amino
acids;
X1—X2(Pro, ProOH)—Gly
 Hydroxy-lysine also occurs in collagen
 The triple helix (tropocollagen) is 300 nm
long and 1.5 nm in diameter
 Held together by H-bonding
 Each strand have ≈800 amino acids (300KDa)
Collagen, types & diseases
 Collagen I: skin, tendon, vessels,
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bone
Collagen II: cartilage
Collagen III: reticular fibers,
alongside type I
Collagen IV: basement
membrane
Collagen V: cell surfaces, hair
and placenta
Cross-linked intra- & inter-molecularly
Cross-linking amounts varies according to
tissue & increases with age
Deficiency of cross-linking (Scurvy &
osteogenesis imperfecta)
Keratin
• Principal component
of epidermis and
related appendages
(hair, horn, nails, &
feathers)
• α(mammals) or β(birds
& reptiles)
• Mammals: ≈30 types,
tissue-specific
• Structure: α-helix,
coiled coil
Elastin
• Rich in hydrophobic amino
acids (ex. Gly, Val & Pro);
mobile hydrophobic regions
bonded by crosslinks
between Lys
• Elastic fibers in arteries are
composed mainly of elastin
(≈70%)
• Tropoelastin → Elastin (Lysyl
oxidase)
Elastin & hydroxylysine
• Collagen contain lysine that can be
hydroxylated by lysyl-hydroxylase to form
hydroxyl-lysine or by lysyl-oxidase to form
Allysine
• Cross-linking of elastin occurs through the
enzyme lysyl-oxidase producing the Allysine,
the pathway for oxidation through lysylhydroxylase does not occur in elastin