FIBROUS PROTEINS

FAIZA ASGHAR

OVER VIEW

• THESE ARE BASIC STRUCTURAL ELEMENTS.

• FIBROUS PROTEINS ARE USUALLY INSOLUBLE .

• THEY ARE FOUND AS COMPONENTS OF SKIN, CONNECTIVE

TISSUE, BLOOD VESSELS, SCLERA AND CORNEA OF EYE.

OVER VIEW

• FIBROUS PROTEINS HAVE HIGH A-HELIX OR B-SHEET CONTENT.

• EXAMPLES INCLUDE:

COLLAGEN

ELASTIN

KERATIN

FIBROIN

COLLAGEN

BASIC INFORMATION

Derived from Greek word “kolla” meaning “Glue Producer”

Most abundant Fibrous protein (structural protein) in vertebrates

25% or more(up to 35%) of total body protein

Major component of connective tissue

Provides an extracellular framework for Strength & Flexibility

At least 19 distinct types of Collagen

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TYPES OF COLLAGEN

•THE TYPES OF COLLAGEN ARE DESIGNATED BY ROMAN NUMERALS.

•THE COLLAGEN GENES ARE NAMED ACCORDING TO THE COLLAGEN TYPE, WRITTEN IN ARABIC NUMERALS FOR THE GENE SYMBOL, FOLLOWED BY AN A AND THE NUMBER OF THE PRO Α CHAIN THAT THEY ENCODE. THUS, THE COL1A1 AND COL1A2 GENES ENCODE THE Α1 AND Α2 CHAINS OF TYPE I COLLAGEN, RESPECTIVELY.

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STRUCTURE OF COLLAGEN

Amino acid sequence

Triple-helical structure

Hydroxyproline and

HydroxylysineGlycosylation

1… AMINO ACID SEQUENCE:

COLLAGEN IS A GLYCOPROTEIN CONTAINING GALACTOSE AND GLUCOSE AS

THE CARBOHYDRATE CONTENT.

GLYCINE IS ONE - THIRD OF TOTAL AMINO ACID CONTENT OF COLLAGEN

FOLLOWED BY HYDROXYPROLINE AND PROLINE

• GLYCINE IS THE PART OF THE REPEATING SEQUENCE.

GLY- X-Y

• X- IS FREQUENTLY PROLINE

• Y- HYDROXY PROLINE OR HYDROXYLYSINE.

•PROLINE - FACILITATE THE FORMATION OF HELICAL

CONFORMATION OF Α- CHAIN, BECAUSE ITS RING

STRUCTURE CAUSES KINK IN THE PEPTIDE CHAIN.

• GLYCINE- FOUND IN EVERY THIRD POSITION OF THE

POLYPEPTIDE CHAIN. IT FITS INTO THE RESTRICTED

SPACES WHERE THE THREE CHAINS OF THE HELIX COME

TOGETHER.

2… TRIPLE- HELICAL STRUCTURE

• AMINO ACIDS SIDE CHAINS ARE ON THE SURFACE OF THE

TRIPLE HELICAL MOLECULE.

• THIS ALLOWS BOND FORMATION BETWEEN THE EXPOSED

R- GROUPS OF NEIGHBORING COLLAGEN MONOMERS-

THIS LEADS TO AGGREGATION INTO FIBRILS.

HYDROXYPROLINE & HYDROXYLYSINE:

HYDROXYLATION OF PROLINE & LYSINE RESIDUES AFTER THEIR INCORPORATION INTO THE POLYPEPTIDE CHAINS.

THUS CALLED POST TRANSLATIONAL MODIFICATION.

CAUSES STABILIZATION OF TRIPLE HELICAL STRUCTURE.

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Proline3-Hydroxyproline

4-Hydroxyproline

Glycine

NH2

| NH2 – CH2 – CH – CH2 – CH2 - C – H | COOH

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Lysine

5-Hydroxylysine

GLYCOSYLATION

• HYDROXYL GROUP OF HYDROXYLYSINE RESIDUES OF COLLAGEN ARE ENZYMATICALLY GLYCOSYLATED.

• MOST COMMONLY GLUCOSE AND GALACTOSE ARE ATTACHED.

BIOSYNTHESIS

OF COLLAGEN

BIOSYNTHESIS OF COLLAGEN

PRECURSORS:

COLLAGEN IS ONE OF THE PROTEINS THAT FUNCTIONS OUTSIDE

THE CELL.

POLYPEPTIDE PRECURSORS OF THE COLLAGEN MOLECULE ARE

FORMED IN FIBROBLAST, OSTEOBLASTS AND CHONDROBLASTS.

THESE ARE SECRETED INTO THE EXTRACELLULAR MATRIX.

Formation of Pro- α-chains

Hydroxylation

Glycosylation

Assembly and Secretion

Extracellular cleavage of Procollagen

molecules

Formation of collagen fibrils

Cross-link formation

FLOWCHART OF COLLAGEN SYNTHESIS

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Glucosyl & Galactosyl added by glycosyl transfarase & galactosyl transfarase.

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Synthesis Of Collagen

USES OF COLLAGEN

• HISTORY:-

• FROM THE GREEK FOR GLUE, KOLLA, THE WORD COLLAGEN MEANS "GLUE PRODUCER".

• COLLAGEN ADHESIVE WAS USED BY EGYPTIANS ABOUT 4,000 YEARS AGO, AND NATIVE AMERICANS USED IT IN BOWS ABOUT 1,500 YEARS AGO. THE OLDEST GLUE IN THE WORLD, CARBON-DATED AS MORE THAN 8,000 YEARS OLD, WAS FOUND TO BE COLLAGEN — USED AS A PROTECTIVE LINING ON ROPE BASKETS AND EMBROIDERED FABRICS, AND TO HOLD UTENSILS TOGETHER; ALSO IN CRISSCROSS DECORATIONS ON HUMAN SKULLS.

INDUSTRIAL USES

• IF COLLAGEN IS PARTIALLY HYDROLYZED, THE THREE TROPOCOLLAGEN

STRANDS SEPARATE INTO GLOBULAR, RANDOM COILS, PRODUCING

GELATIN, WHICH IS USED IN MANY FOODS, INCLUDING FLAVORED GELATIN

DESSERTS. BESIDES FOOD, GELATIN HAS BEEN USED IN PHARMACEUTICAL,

COSMETIC, AND PHOTOGRAPHY INDUSTRIES.

• ANIMAL GLUES ARE THERMOPLASTIC, SOFTENING AGAIN UPON REHEATING,

AND SO THEY ARE STILL USED IN MAKING MUSICAL INSTRUMENTS SUCH AS

FINE VIOLINS AND GUITARS.

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MEDICAL USES:-

• COLLAGENS ARE WIDELY EMPLOYED IN THE CONSTRUCTION OF ARTIFICIAL SKIN SUBSTITUTES USED IN THE MANAGEMENT OF SEVERE BURNS & BEAUTY TREATMENTS.

• (THESE COLLAGENS MAY BE DERIVED FROM BOVINE, PORCINE, AND EVEN HUMAN SOURCES AND ARE SOMETIMES USED IN COMBINATION WITH SILICONES, GLYCOSAMINOGLYCANS, FIBROBLASTS, GROWTH FACTORS AND OTHER SUBSTANCES)

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• COLLAGEN IS ALSO SOLD COMMERCIALLY AS A JOINT MOBILITY SUPPLEMENT.  

• COLLAGEN IS NOW BEING USED AS A MAIN INGREDIENT FOR SOME COSMETIC

MAKEUP.

• RECENTLY AN ALTERNATIVE TO ANIMAL-DERIVED COLLAGEN HAS BECOME

AVAILABLE. ALTHOUGH EXPENSIVE, THIS HUMAN COLLAGEN, DERIVED FROM

DONOR CADAVERS, PLACENTAS AND ABORTED FETUSES, MAY MINIMIZE THE

POSSIBILITY OF IMMUNE REACTIONS.

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COLLAGEN IN WOUND HEALING

• VITAL ROLE IN HEMOSTASIS

• ATTRACTS THROMBOCYTES

• ACTIVATES THROMBOCYTES TO SECRETE SEROTONIN,

ADP AND THROMBOXANE A2

• PLATELET PLUG IS FORMED

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CHANGES IN COLLAGEN DUE TO AGEING

• INCREASE IN PYRIDINOLINE AND DEOXYPYRIDINOLINE

• INCREASE IN THE THICKNESS OF COLLAGEN FIBER

• INCREASE IN LENGTH

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CHARACTERISTICS

HAIR WHITENING WRINKLING AND TOUGHENING OF NAILS WRINKLING AND TOUGHENING OF SKIN

ABNORMALITIES ASSOCIATED WITH COLLAGEN

•EHLERS-DANLOS SYNDROME

- GROUP OF INHERITED DISEASE

- COLLAGEN INVOLVED III-

CHARACTERISTICS

- HYPER EXTENSIBILITY OF SKIN.

- ABNORMAL TISSUE FRAGILITY

-INCREASE JOINT MOBILITY

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OSTEOGENESIS IMPERFECTA

CAUSED DUE TO ABNORMAL (LESS) COLLAGEN TYPE I

CHARACTERISTICS

- WEAK BONES

- FRAGILE BONES

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EPIDERMOLYSIS BULLOSADUE TO ALTERATION OF COLLAGEN TYPE VII

CHARACTERISTICS

- SKIN BREAKS

- BLISTER FORMATION

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SCURVY• GLY –X- Y (Y = 4-HYDROXYPROLINE)

• ENZYME : PROPYL-4-HYDROXYLASE

CO-FACTOR: VIT. C. DUE TO VIT C DEFICIENCY

(IMPAIRED SYNTHESIS OF COLLAGEN DUE TO

DEFICIENCIES OF PROLYL AND LYSYL HYDROXYLASES)

CHARACTERISTICS-

- BLEEDING GUM

- DELAYED WOUND HEALING

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GENETIC DISEASES DUE TO COLLAGEN SYNTHESIS ABNORMALITIES-DUE TO

GENE MUTATION

Gene or Enzyme

Disease

COL1A1,COL1A2 Osteogenesis imperfecta, osteoporosis, ehlers-danlos syndrome type VII

COL2A1 Severe chondrodysplasia osteoarthritis

COL3A1 Ehlers-danlos syndrome type IV

COL4A3-COL4A6 Alport syndrome (including both autosomal and X-linked forms)

COL7A1 Epidermolysis bullosa, dystrophic

COL10A1 Schmid metaphysial chondrodysplysia

Lysyl hydroxylase

Ehlers-danlos syndrome type VI

Propcollagen N-proteinase

Ehlers-danlos syndrome type VII autosomal recessive

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Fibrous vs. Globular Proteins

1. Compact protein structure Extended protein structure

2. Soluble in water (or in lipid Insoluble in water (or in lipid bilayers) bilayers)

3. Secondary structure is complex Secondary structure is simplewith a mixture of a-helix, b-sheet based on one type onlyand loop structures 4. Quaternary structure is held Quaternary structure is usually together by noncovalent forces held together by covalent bridges

5. Functions in all aspects of Functions in structure of the body metabolism (enzymes, transport, or cell (tendons, bones, muscle, immune protection, hormones, etc). ligaments, hair, skin)

Globular Fibrous

• A PROTEIN IS IN ITS NATIVE CONFORMATION WHEN 

1. IT IS THERMODYNAMICALLY LEAST STABLE.

2. IT HAS THE HIGHEST GIBBS FREE ENERGY.

3. IT IS IN ANY OF ITS FUNCTIONAL, FOLDED STATES.

4. IT IS UNFOLDED

• HYDROGEN BONDS BETWEEN AMINO ACIDS IN A POLYPEPTIDE OCCUR BETWEEN WHICH CHEMICAL

GROUPS? 

1. THE C=O AND C-H GROUPS

2. THE C=O AND C-R GROUPS

3. THE C=O GROUPS

4. THE C-R AND C-R GROUPS

 

Ans: 3

Ans: 1

• PROLINE RESIDUES ARE MOST LIKELY TO OCCUR IN WHICH OF THE FOLLOWING SECONDARY

STRUCTURES?

1. AN Α HELIX

2. A Β TURN

3. A Β SHEET

4. A COILED COIL

• FIBROUS PROTEINS DIFFER FROM GLOBULAR PROTEINS IN THE:

1. FIBROUS PROTEINS TEND TO SERVE STRUCTURAL FUNCTIONS, AND GLOBULAR PROTEINS ARE

MORE LIKELY TO BE ENZYMES

2. FIBROUS PROTEINS CAN OFTEN CONTAIN SEVERAL TYPES OF SECONDARY STRUCTURE, WHEREAS

GLOBULAR PROTEINS USUALLY CONSIST LARGELY OF A SINGLE TYPE OF SECONDARY STRUCTURE

3. GLOBULAR PROTEINS ARE INSOLUBLE IN WATER, AND FIBROUS PROTEINS ARE USUALLY SOLUBLE

4. GLOBULAR PROTEINS ARE MORE LIKELY THAN FIBROUS PROTEINS TO HAVE AN ELABORATE

QUATERNARY STRUCTURE

Ans: 2

Ans: 1

• WHY IS THE Α-HELIX CONFORMATION IN POLYPEPTIDES SUCH A STABLE FORM? 

1.THE Α HELIX STRUCTURE IS STABILIZED BY HYDROPHOBIC INTERACTIONS

2.THE Α HELIX STRUCTURE IS STABILIZED BY HYDROGEN BONDS

3.THE Α HELIX STRUCTURE IS STABILIZED BY DISULFIDE BONDS

4.THE Α HELIX STRUCTURE IS STABILIZED BY PROLINE RESIDUES

 

• A PROTEIN IN SOLUTION IS MORE LIKELY TO MAINTAIN ITS NATIVE CONFORMATION

WHEN 

1.THE NUMBER OF HYDROGEN BONDS WITHIN A PROTEIN IS MINIMIZED

2.THE NUMBER OF HYDROGEN BONDS WITH WATER MOLECULES IS MAXIMIZED

3.THE PROTEIN IS LEAST STABLE

4. ITS HYDROPHOBIC RESIDUES ARE LARGELY BURIED IN THE PROTEIN INTERIOR

Ans: 4

Ans: 2

• WHICH BONDS ARE PLANAR (CANNOT ROTATE) IN A POLYPEPTIDE BACKBONE?

1.CΑ-C BONDS

2.C-N BONDS

3.N-CΑ BONDS

4.CΑ-CΑ BONDS

 

• IF HELICAL RISE PER AMINO ACID IS 1.5 Å AND LENGTH OF POLYPEPTIDE IS 20 Å, THEN HOW

MANY AMINO ACIDS ARE PRESENT IN THE Α-HELIX?

1. 30 AMINO ACIDS

2. 17 AMINO ACIDS

3. 13 AMINO ACIDS

4. 9 AMINO ACIDS

Ans: 2

Ans: 3

• IF THERE ARE 101 AMINO ACIDS, THEN HOW MANY BONDS ARE PRESENT AROUND WHICH ROTATION

CAN OCCUR?

1. 101 BONDS

2. 202 BONDS

3. 303 BONDS

4. 505 BONDS

 

• WHICH IS THE REPEATING UNIT IN COLLAGEN?

1. GLY-X-PRO

2. PRO-GLY-X

3. X-PRO-GLY

4. ALL OF THE ABOVE

5. NONE OF THE ABOVE

 

Ans: 2

Ans: 4

• WHAT IS THE NUMBER OF AMINO ACIDS PER TURN IN Β-SHEETS?

1. 1

2. 2

3. 4

4.NONE OF THESE

 

• Β-BULGE IS FORMED BECAUSE OF

1.EXTRA AMINO ACID(S) IN LONGER POLYPEPTIDE

2.EXTRA AMINO ACID(S) IN SHORTER POLYPEPTIDE

3.PROLINE IN THE BULGE

4.NONE OF THE ABOVE

Ans: 3

Ans: 1

†ħåñk ÿØû

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