[008] Connective Tissue Fibrous Proteins: Shape and Function (α-Keratin, Elastin, Collagen) Flashcards
The CT’s ECM is made of ?
1)Water
2)minerals
3)proteoglycans
4) fibrous proteins
Main properties of fibrous proteins?
Extended protein structure.
Insoluble in water.
Secondary structure is simple based on one type.
Quaternary structure is it together by covalent Bridges.
Secondary structureOf alpha Keratin ?
Alpha helix
SuperSecondary Structure of Alpha Keratin ?
1)TWO parallel α -helices supercoil around each other to form a dimer
2) Each dimer associates antiparallel with another dimer in a staggered arrangement to form the protofibril.
The following picture shows the structure of Alpha Keratin , mention the hidden.
…. Is a rubber like protein
Elastin
… & … cells synthesize elastin
FibroblastsAnd chondrocytes
Where can elastin be found ?
elastic ligaments,
lung walls
blood vessel walls (large arteries, e.g. the aorta)
Diseases implicated with Elastin synthesis errors ?
Emphysema and CVDs
…. Is the building unit of Elastin.
tropoelastin
… secretes tropoelastin ?
Cells of ECM
AA. Composition of elastin ?
1) Rich in lysine
2) and Allysine
3) They form large hydrophobic peptides
… is an aldehyde form of lysine
Allysine
…. (Protein) is rich in allysine.
Elastine
… (enzyme) oxidatevly-deaminates lysine to Allysine.
lysine oxidase
Function of large hydrophobic peptides present in Elastine
Their sidechains do not interact with each other by hydrogen bonds, and their role appears to allow the elastin network to deform.
How Tropoelastin forms Elastin ?
crosslinking of tropoelastin via lysine residues gives elastin extensive interconnection leading to a rubbery consistency
This figure shows a type of crosslinking that takes place in formation of Elastin , mention the name of this link.
desmosine link (4 Lysine residues)
This figure shows a type of crosslinking that takes place in formation of Elastin , mention the name of this link.
-lysinonorleucine link (2 Lysine residues)
linking 2 tropoelastin molecules
Mention the exact structure of the Desmosine cross-links in Elastin.
Formed of three allysine (modified lysine) plus one lysine residue.
…. Is the most abundant protein in the body.
Collagen
Mention the formation of type one Collagen
formed of 2 α1 chains and 1 α2 chain.
… &…(cells) makes collagen
fibroblasts and chondrocytes
… is the building unit of Collagen.
Tropocollagen
Tropocollagen is formed of ?
three coiled peptides [left-hand α-chains] , tightly twisted to form a right handed superhelix.
AA. Composition of tropocollagen ?
α-chain contains the repeating triplet sequence Gly-X-Y :
-The X position is ussually occupied by proline , sometimes lysine
-The y position is ussually occupied by hydroxyproline , sometimes hydroxylysine
….(fibrous protein) is considered a a glycoprotein
Collagen
…&…(sugar) molecules are attached to hydroxylysine residues in Collagen.
Glucose and galactose
…(AA. In collagen) is responsible for collagen’s glycosilation.
hydroxylysine
Why Collagen has a strong structure ?
1-Each turn contains 3 amino acid residues (makes a tight helix), normal proteins contain 3.3 a.a. / turn.
2- The presence of glycine with its short side chain makes the polypeptide chains very close to each other.
4-The high content of hydroxyproline forms hydrogen bonds between chains
5-The formation of covalent cross linkages between adjacent polypeptide chains is responsible for tensile properties of collagen.
most common types of collagen ?
type I and type II.
Type I Collagen consists of ?
(2 α1,, 1α2),
Type II Collagen consists of ?
(3α1)
Four stages of collagen assembly ?
(1) Synthesized as procollagen which is secreted from the cell
(2) Cleaved to tropocollagen by procollagen peptidase
(3) Assembly of tropocollagen leads to formation of the collagen fiber
4) Chemical crosslinking of tropocollagen strengthens the fiber
Mention steps of procollagen formation
• The 3 separate pro-α chains are synthesized inside the cell.
• Selected Pro and Lys residues are hydroxylated to Hyp and Hyl
• Selected hydroxylysine residues are glycosylated
• Three pro-α chains assemble at the C-terminus end starting with disulphide bridge formation between the 3 chains.
• The 3 chains then “zip” up to form procollagen.
• Three pro-α chains assemble at the …terminal end through …. (Bond) formation between the 3 chains.
C-terminal— disulphide bridge formation
The figure shows an intermidiate structure in collagen formation ?
Procollagen
…. Is a medical problem related to the formation of Procollagen
osteogenesis imperfecta
Second stage of collagen formation ?
Cleavage of procollagen to tropocollagen
….(enzyme) cleaves procollagen to tropocollagen.
procollagen peptidase
Mention the secondary structure of tropocollagen
triple helix
…. Is a medical problem related to tropocollagen formation
Ehlers-Danlos syndrome
Third stage of collagen formation ?
Assembly of tropocollagen
Explain the assembly of tropocollagen
• The formation of a one-quarter staggered array of tropocollagen molecules
• There are (40 nm) gaps between the tropocollagen molecules which is where calcium phosphate is deposited in bone formation
• This assembly forms spontaneously by means of noncovalent hydrogen bond interactions involving the OH group of hydroxyproline
The following figure illustrates a step in collagen formation , explain it
• The formation of a one-quarter staggered array of tropocollagen molecules (i.e. each of which is displaced lengthwise by a quarter of its length)
• There are (40 nm) gaps between the tropocollagen molecules which is where calcium phosphate is deposited in bone formation
• This assembly forms spontaneously by means of noncovalent hydrogen bond interactions involving the OH group of hydroxyproline
… is a medical condition related to the 3rd step of collagen formation
Scurvy
Fourth stage of collagen formation is ?
Crosslinking of collagen fiber
Explain the Fourth stage of collagen formation
-Crosslinking of collagen fiber
- Collagen fibre is stabilized by covalent crosslinks between lysine residues.
… is a medical problem related to the Crosslinking of collagen fiber (4th stage)
lathyrism
…. Is alo known as brittle bone syndrome.
Osteogenesis imperfecta
Pathogenesis of Osteogenesis imperfecta ?
-Results from a mutant collagen gene: a buried Glycine residue is mutated to Cystein in procollagen
• The triple helix is partially unfolded at the N-terminal end
• The tropocollagen subunits are not tightly packed, and collagen fiber formation is weaker
• Patients suffer from skeletal deformities
Manifestations of Osteogenesis Imperfecta ?
• deformed bones which can easily be fractured
• slight spinal curvature
• loose joints
• long tapering extremities
• poor muscle tone
• sometimes with hearing loss or blue sclerae
Pathogensis of Ehlers-Danlos syndrome ?
• Results from reduced levels of procollagen peptidase, so procollagen is not fully converted into tropocollagen
• A high level of procollagen is found in the skin and tendons of patients
• The 40 nm gaps between tropocollagen molecules become blocked by uncleaved peptides which prevent lysine oxidase from acting on tropocollagen to create the crosslinks (no crosslinks)
Ehlers-Danlos syndrome patients suffer from ?
stretchable skin
-hypermobile joints
-short stature
…. Is also called the famous disease of medieval Europe
Scurvy
Pathogenesis of Scurvy ?
• is related to assembly of tropocollagen
• Hydroxyproline is important for the correct assembly of collagen fibers.
• Hydroxyproline is only formed from Proline residues after procollagen has been formed.
• This reaction of Proline with proline hydroxylase requires ascorbate (Vitamin C) as a cofactor
• Complications of scurvy ?
• poor collagen fibril formation
• skin lesions develop and wounds do not heal
• blood vessel walls are fragile
• bleeding under the skin and in gums
• falling of teeth
…. Is another form of Ehlers Danlos syndrome.
Lathyrism
Pathogenesis of Lathyrism ?
A Diet induced disease Caused by inhibition of lysine oxidase by:
• ingestion of sweet pea seeds(contain β-aminopropionitrile)
• may be due to copper deficiency in diet This affects the cross-linking of collagen
Lathyrism is Characterized by:
• Deformation of spine
• Dislocation of joints
• Demineralization of bones
• Joint hemorrhage
• Aortic aneurism
