Fibrous & Globular Proteins: For BDS-1st Yr

FIBROUS & GLOBULAR PROTEINS
For BDS-1st Yr
Dr Umer Saeed Ansari

Assistant Professor Biochemistry LMDC
MBBS (King Edward Medical College)
M.Phil, PhD biochemistry
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FIBROUS PROTEINS
What are fibrous proteins?
• These are proteins which have an axial ratio

greater than 10
• Axial ratio = molecular length/width
• Fibrous proteins exhibit long, thread-like
molecules forming elongated fibers or sheets
COLLAGEN
Most abundant protein
COLLAGEN HAS 3 PEPTIDE CHAINS
• Collagen molecule is a long, rigid structure in

which three polypeptides (3 α chains) are
wound around one another in a rope-like triple
helix
• Collagen belongs to a group of proteins called
ALBUMINOIDS (scleroproteins)
STRUCTURAL FEATURES
(Glycine-X-Y)
• Collagen has a high content of GLYCINE amino

acid (every 3rd amino acid; 32-35%) Proline &
hydroxyproline make up another 25% of the
amino acids present
• Collagen is deficient in TRYPTOPHAN
PROLINE FORMS THE ‘KINKS’
• Proline facilitates the formation of α helical

conformation by its ring structure, and
produces ‘kinks’ or ‘bends’ in the polypeptide
α chains
HYDROXYPROLINE & HYDROXYLYSINE
• These are formed by hydroxylation of some of

the proline & lysine residues after their
incorporation into the polypeptide chains
BIOSYNTHESIS OF COLLAGEN
• The polypeptide precursors of the collagen

molecule are synthesized in the FIBROBLASTS
• These precursor polypeptide chains are then
modified by enzymes, and form the triple helix
• These are then secreted into the ECM
STEP-1
FORMATION OF PRE-PRO-α CHAINS
• The polypeptide precursors of α chains are

called as PRE-PRO-α CHAINS which contain a
special amino acid sequence at their N-
terminal ends (signal sequence)
• This signal sequence directs the passage of
pre-pro α chains into the RER
STEP-2
FORMATION OF PRO-α CHAINS
• These pre-pro-α chains enter the lumen of the

rough endoplasmic reticulum (RER)
• The signal sequence is cleaved in the RER, to
yield PRO-α-CHAINS
STEP- 3
HYDROXYLATION OF PROLINE & LYSINE
• Proline & Lysine undergo hydroxylation to

form HYDROXYPROLINE & HYDROXYLYSINE
• These hydroxylations require molecular
oxygen and VITAMIN C
STEP- 4
GLYCOSYLATION OF HYDROXYLYSINE
• Some hydroxylysine residues are modified by
glycosylation with glucose (or glucosyl-
galactose units)
STEP- 5
FORMATION OF PROCOLLAGEN
• After hydroxylation & glycosylation, the three
pro-α chains form PROCOLLAGEN
• There is formation of inter-chain disulfide
linkages bringing the pro-α chains in
alignment for helix formation
STEP- 6
FORMATION OF TROPOCOLLAGEN
• In the extracellular space, these procollagen

molecules are cleaved by Procollagen
Peptidases, which cleave procollagen to form
TROPOCOLLAGEN
STEP- 7
FORMATION OF COLLAGEN FIBRILS
• Tropocollagen molecules associate themselves

to form COLLAGEN FIBRILS
STEP- 8
CROSS-LINK FORMATION
• A copper containing enzyme Lysyl Oxidase
oxidatively deaminates some of the lysine &
hydroxylysine residues, resulting in formation
of covalent cross-links, thus MATURE
COLLAGEN fibers are formed
COLLAGEN DISEASES
(Collagenopathies)
Collagenopathies
• Defects in any one of the many steps in
synthesis of collagen results in genetic disease
characterized by defective collagen formation
• These include: EHLERS DANLOS SYNDROME &
OSTEOGENESIS IMPERFECTA
EHLERS-DANLOS SYNDROME
(EDS)
• It is a heterogenous group of connective tissue
disorders
• CAUSE: deficiency of Lysyl Oxidase enzyme, or,
Pro-collagen Peptidase, or, from mutations in
amino acid sequences in collagen types I, III or
V
CLASSIC FORM OF EDS
• There is defect in TYPE V collagen

• Patient has marked skin extensibility & fragility
and joint hyper-mobility
VASCULAR FORM OF EDS
• It is the most serious form of EDS
• Defect in type III collagen therefore, it may

cause life-threatening rupture of blood vessels
(Brittle-bone disease)
• It is a genetic disease of bone fragility,

characterized by bones which fracture easily,
with minor trauma
• It is caused by mutations that code for α1 or
α2 chains in Type I collagen
• Most common mutations cause the

replacement of glycine by amino acids having
bulky side chains
• Type I: bone fragility, hearing loss and blue

sclera
• Type II: bone fragility, intra-uterine fractures
and pulmonary complications
• Type III: multiple fractures at birth, short
stature, spinal curvature and blue sclera

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FIBROUS & GLOBULAR PROTEINS

Dr Umer Saeed Ansari

• These are proteins which have an axial ratio

• Collagen molecule is a long, rigid structure in

• Collagen has a high content of GLYCINE amino

• Proline facilitates the formation of α helical

• These are formed by hydroxylation of some of

• The polypeptide precursors of the collagen

• The polypeptide precursors of α chains are

• These pre-pro-α chains enter the lumen of the

• Proline & Lysine undergo hydroxylation to

• Some hydroxylysine residues are modified by

glycosylation with glucose (or glucosyl-

• In the extracellular space, these procollagen

• Tropocollagen molecules associate themselves

• There is defect in TYPE V collagen

• It is the most serious form of EDS

• Defect in type III collagen therefore, it may

• It is a genetic disease of bone fragility,

• Most common mutations cause the

• Type I: bone fragility, hearing loss and blue

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