[008] Connective Tissue Fibrous Proteins: Shape and Function (α-Keratin, Elastin, Collagen)

Question 1

The CT’s ECM is made of ?

Answer 1

1)Water
2)minerals
3)proteoglycans
4) fibrous proteins

Question 2

Main properties of fibrous proteins?

Answer 2

Extended protein structure.

Insoluble in water.

Secondary structure is simple based on one type.

Quaternary structure is it together by covalent Bridges.

Question 3

Secondary structureOf alpha Keratin ?

Answer 3

Alpha helix

Question 4

SuperSecondary Structure of Alpha Keratin ?

Answer 4

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.

Question 5

The following picture shows the structure of Alpha Keratin , mention the hidden.

Answer 5

Question 6

…. Is a rubber like protein

Answer 6

Elastin

Question 7

… & … cells synthesize elastin

Answer 7

FibroblastsAnd chondrocytes

Question 8

Where can elastin be found ?

Answer 8

elastic ligaments,
lung walls
blood vessel walls (large arteries, e.g. the aorta)

Question 9

Diseases implicated with Elastin synthesis errors ?

Answer 9

Emphysema and CVDs

Question 10

…. Is the building unit of Elastin.

Answer 10

tropoelastin

Question 11

… secretes tropoelastin ?

Answer 11

Cells of ECM

Question 12

AA. Composition of elastin ?

Answer 12

1) Rich in lysine
2) and Allysine
3) They form large hydrophobic peptides

Question 13

… is an aldehyde form of lysine

Answer 13

Allysine

Question 14

…. (Protein) is rich in allysine.

Answer 14

Elastine

Question 15

… (enzyme) oxidatevly-deaminates lysine to Allysine.

Answer 15

lysine oxidase

Question 16

Function of large hydrophobic peptides present in Elastine

Answer 16

Their sidechains do not interact with each other by hydrogen bonds, and their role appears to allow the elastin network to deform.

Question 17

How Tropoelastin forms Elastin ?

Answer 17

crosslinking of tropoelastin via lysine residues gives elastin extensive interconnection leading to a rubbery consistency

Question 18

This figure shows a type of crosslinking that takes place in formation of Elastin , mention the name of this link.

Answer 18

desmosine link (4 Lysine residues)

Question 19

This figure shows a type of crosslinking that takes place in formation of Elastin , mention the name of this link.

Answer 19

-lysinonorleucine link (2 Lysine residues)
linking 2 tropoelastin molecules

Question 20

Mention the exact structure of the Desmosine cross-links in Elastin.

Answer 20

Formed of three allysine (modified lysine) plus one lysine residue.

Question 21

…. Is the most abundant protein in the body.

Answer 21

Collagen

Question 22

Mention the formation of type one Collagen

Answer 22

formed of 2 α1 chains and 1 α2 chain.

Question 23

… &…(cells) makes collagen

Answer 23

fibroblasts and chondrocytes

Question 24

… is the building unit of Collagen.

Answer 24

Tropocollagen

Question 25

Tropocollagen is formed of ?

Answer 25

three coiled peptides [left-hand α-chains] , tightly twisted to form a right handed superhelix.

Question 26

AA. Composition of tropocollagen ?

Answer 26

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

Question 27

….(fibrous protein) is considered a a glycoprotein

Answer 27

Collagen

Question 28

…&…(sugar) molecules are attached to hydroxylysine residues in Collagen.

Answer 28

Glucose and galactose

Question 29

…(AA. In collagen) is responsible for collagen’s glycosilation.

Answer 29

hydroxylysine

Question 30

Why Collagen has a strong structure ?

Answer 30

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.

Question 31

most common types of collagen ?

Answer 31

type I and type II.

Question 32

Type I Collagen consists of ?

Answer 32

(2 α1,, 1α2),

Question 33

Type II Collagen consists of ?

Answer 33

(3α1)

Question 34

Four stages of collagen assembly ?

Answer 34

(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

Question 35

Mention steps of procollagen formation

Answer 35

• 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.

Question 36

• Three pro-α chains assemble at the …terminal end through …. (Bond) formation between the 3 chains.

Answer 36

C-terminal— disulphide bridge formation

Question 37

The figure shows an intermidiate structure in collagen formation ?

Answer 37

Procollagen

Question 38

…. Is a medical problem related to the formation of Procollagen

Answer 38

osteogenesis imperfecta

Question 39

Second stage of collagen formation ?

Answer 39

Cleavage of procollagen to tropocollagen

Question 40

….(enzyme) cleaves procollagen to tropocollagen.

Answer 40

procollagen peptidase

Question 41

Mention the secondary structure of tropocollagen

Answer 41

triple helix

Question 42

…. Is a medical problem related to tropocollagen formation

Answer 42

Ehlers-Danlos syndrome

Question 43

Third stage of collagen formation ?

Answer 43

Assembly of tropocollagen

Question 44

Explain the assembly of tropocollagen

Answer 44

• 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

Question 45

The following figure illustrates a step in collagen formation , explain it

Answer 45

• 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

Question 46

… is a medical condition related to the 3rd step of collagen formation

Answer 46

Scurvy

Question 47

Fourth stage of collagen formation is ?

Answer 47

Crosslinking of collagen fiber

Question 48

Explain the Fourth stage of collagen formation

Answer 48

-Crosslinking of collagen fiber - Collagen fibre is stabilized by covalent crosslinks between lysine residues.

Question 49

… is a medical problem related to the Crosslinking of collagen fiber (4th stage)

Answer 49

lathyrism

Question 50

…. Is alo known as brittle bone syndrome.

Answer 50

Osteogenesis imperfecta

Question 51

Pathogenesis of Osteogenesis imperfecta ?

Answer 51

-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

Question 52

Manifestations of Osteogenesis Imperfecta ?

Answer 52

• 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

Question 53

Pathogensis of Ehlers-Danlos syndrome ?

Answer 53

• 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)

Question 54

Ehlers-Danlos syndrome patients suffer from ?

Answer 54

stretchable skin -hypermobile joints -short stature

Question 55

…. Is also called the famous disease of medieval Europe

Answer 55

Scurvy

Question 56

Pathogenesis of Scurvy ?

Answer 56

• 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

Question 57

• Complications of scurvy ?

Answer 57

• 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

Question 58

…. Is another form of Ehlers Danlos syndrome.

Answer 58

Lathyrism

Question 59

Pathogenesis of Lathyrism ?

Answer 59

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

Question 60

Lathyrism is Characterized by:

Answer 60

• Deformation of spine • Dislocation of joints • Demineralization of bones • Joint hemorrhage • Aortic aneurism