Fibrous and Globular Proteins
Fibrous proteins share properties that give strength and/or flexibility to the structures in which
they occur. In each case, the fundamental structural unit is a simple repeating element of
secondary structure. All fibrous proteins are insoluble in water, a property conferred by a high
concentration of hydrophobic amino acid residues both in the interior of the protein and on its
surface. These hydrophobic surfaces are largely buried by packing many similar polypeptide
chains together to form elaborate supramolecular complexes.e.g., α--Keratin, collagen, and silk
fibroin, etc,.
In a globular protein, different segments of a polypeptide chain (or multiple polypeptide chains)
fold back on each other. this folding generates a compact form relative to polypeptides in a fully
extended conformation. The folding also provides the structural diversity necessary for proteins
to carry out a wide array of biological functions. Globular proteins include enzymes, transport
proteins, motor proteins, regulatory proteins, immunoglobulins, and proteins with many other
functions.e.g,. myoglobin cytochrome c, lysozyme, and ribonuclease
Collagen
collagen is the most abundant protein in human body. It is found in connective tissue such as
tendons, cartilage, the organic matrix of bone, and the cornea of the eye. The collagen helix is a
unique secondary structure quite distinct from the α helix. It is left-handed and has three amino
acid residues per turn. Collagen is also a coiled coil, but one with distinct tertiary and quaternary
structures: three separate polypeptides, called α chains (not to be confused with α helices), are
supertwisted about each other . The superhelical twisting is right-handed in collagen, opposite in
sense to the left-handed helix of the α chains. Collagen superfamily of proteins includes more
than twenty different types, as well as, additional proteins that have collagen like domains.
Fibril forming collagens include types I,II and III and have rope like structures. Type I are found
in supporting elements of high tensile strength like tendon and cornea. Type II are restricted to
collaginous structures and type III are present in more distensible tissues like blood vessels.
Network forming collagens include type IV and VII forming three dimensional meshwork
examples include basement membranes.
Fibril associated collagens include types IX and XII that bind to the surface of collagen fibrils
linking them to one another and to other components in extracellular matrix for example
cartilage type IX and tendon, ligaments type XII
Structure
Collagen is rich in proline and glycine, both of which are important in triple helix formation. Pro
facilitates the formation of helical conformation of each α chain because its ring structures
causes kinks in the polypeptide chain. Glycine is found in every third position of polypeptide
chain. It fits in the restricted spaces where three chains of helix come together. The gly residues
are part of a repeating sequence, -gly-X-Y-, where X is frequently pro and Y is often
hydroxylproline or hydroxylysine.
Collagen contains hydoxypro and hydoxylys, which are not present in most other tissues. These
residues result from hydroxylation of some pro and lys residues after their incorporation into
polypeptide chain as a most translational modification requiring molecular oxygen and vitamin c
and enzymes prolylhydroxylase and lysylhydroxylase respectively. The hydroxylysine residues
may also be enzymatically glycosylated.
Biosynthesis
, The polypeptide precursors of collagen molecule are formed in fibroblasts, osteoblasts and
chondroblasts and secreted into extracellular matrix. Like most proteins produced for export the
newly synthesized α chains of collagen contain signal sequence at N terminal ends which
facilitates the binding of ribosomes to rough endoplasmic reticulum and directs their passage into
RER where signal sequence is cleaved to yield pro α chain of collagen. After hydroxylation and
glycosylation pro α chain form procollagen. The formation of procollagen begins with
formation of interchain disulfide bonds between c-terminal extentions of pro α chain, bringing
the three chains into alignment favourable for helix formation. The rpocollagen molecules are
translocated to golgi where they are packaged into secretory vesicles which fuse with membrane
causing release of procollagen into extracellular space. Here they are cleaved by N and C
procollagen peptidases removing terminal propeptides releasing triple helical collagen
molecules.
The extracellular copper containg enzyme lysyl oxidase oxidatively deaminates some of lysly
and hydroxylys residues in collagen forming reactive aldehydes allysine and hydroxyallysine
which condense with neighbouring lys and hydroxylys residues of other collagen molecules
forming covalent cross links, essential for achieving high tensile strength.
Collagen diseases
Defects in any one of the steps involved in collagen synthesis results in diseases involving an
inability to form fibres properly. More than 1000 mutations have been detected in 22 genes
coding for twelve of collagen types.
1) Ehlers danlos syndrome ; heterogenous group of generalized connective tissues disorders
resulting from inheritable defects in metabolism of collagen. EDS can result from a
defiency of collagen processing enzymes like lysly hydroxylase or mutations in amino
acid sequences of collagen type I,II or IV. These patients have stretchy skins and loose
joints as in case Indian rubber man.
2) Osteogensis inperfecta; also known as brittle bone syndrome, is also a heterogenous
group of inherited disorders distinguished by bones that easily bend and fracture.
Retarded wound healing and humped back appearance are common features of this
diseses. Most patients have mutations in gene coding for pro 1 or pro 2 alpha chains of
type I collagen and the most common one is substitution of bulky side chain amino acid
for gly preventing proper folding of triple helix.
Elastin
Elastin is a connective tissue protein having rubber like properties. Elastic fibers of elastin are
composed of elastin and glucoprotein microfibrils are found in the lungs, walls of large arteries
and elastic ligaments. Elastin is a insoluble polymer synthesized from a precursor troelastin
which is a linear polypeptide of about 700 amino acids that are primarily small and nonpolar.
Elastin is rich in pro and lys but contains only a little hydroxypro and no hydroxylys.
Tropoelastin is secreted by the cell into extracellular space where it interacts with fibrillin which
acts as a scaffold onto which tropoelastin is deposited. Some of the lys side chains are
oxidatively deaminated by lysyl oxidase forming allysine, three of which plus one unaltered lys
side chain from same or neighbouring polypeptide forms a desmosine like cross link, which
produces elastin- an extensivel crosslinked rubbery network that can stretch bend in any
direction when stressed, giving connective tissues elasticity.
α-Keratin
The α-keratins have evolved for strength. Found in mammals, these proteins constitute almost
the entire dry weight of hair, wool, nails, claws, quills, horns, hooves, and much of the outer
Fibrous proteins share properties that give strength and/or flexibility to the structures in which
they occur. In each case, the fundamental structural unit is a simple repeating element of
secondary structure. All fibrous proteins are insoluble in water, a property conferred by a high
concentration of hydrophobic amino acid residues both in the interior of the protein and on its
surface. These hydrophobic surfaces are largely buried by packing many similar polypeptide
chains together to form elaborate supramolecular complexes.e.g., α--Keratin, collagen, and silk
fibroin, etc,.
In a globular protein, different segments of a polypeptide chain (or multiple polypeptide chains)
fold back on each other. this folding generates a compact form relative to polypeptides in a fully
extended conformation. The folding also provides the structural diversity necessary for proteins
to carry out a wide array of biological functions. Globular proteins include enzymes, transport
proteins, motor proteins, regulatory proteins, immunoglobulins, and proteins with many other
functions.e.g,. myoglobin cytochrome c, lysozyme, and ribonuclease
Collagen
collagen is the most abundant protein in human body. It is found in connective tissue such as
tendons, cartilage, the organic matrix of bone, and the cornea of the eye. The collagen helix is a
unique secondary structure quite distinct from the α helix. It is left-handed and has three amino
acid residues per turn. Collagen is also a coiled coil, but one with distinct tertiary and quaternary
structures: three separate polypeptides, called α chains (not to be confused with α helices), are
supertwisted about each other . The superhelical twisting is right-handed in collagen, opposite in
sense to the left-handed helix of the α chains. Collagen superfamily of proteins includes more
than twenty different types, as well as, additional proteins that have collagen like domains.
Fibril forming collagens include types I,II and III and have rope like structures. Type I are found
in supporting elements of high tensile strength like tendon and cornea. Type II are restricted to
collaginous structures and type III are present in more distensible tissues like blood vessels.
Network forming collagens include type IV and VII forming three dimensional meshwork
examples include basement membranes.
Fibril associated collagens include types IX and XII that bind to the surface of collagen fibrils
linking them to one another and to other components in extracellular matrix for example
cartilage type IX and tendon, ligaments type XII
Structure
Collagen is rich in proline and glycine, both of which are important in triple helix formation. Pro
facilitates the formation of helical conformation of each α chain because its ring structures
causes kinks in the polypeptide chain. Glycine is found in every third position of polypeptide
chain. It fits in the restricted spaces where three chains of helix come together. The gly residues
are part of a repeating sequence, -gly-X-Y-, where X is frequently pro and Y is often
hydroxylproline or hydroxylysine.
Collagen contains hydoxypro and hydoxylys, which are not present in most other tissues. These
residues result from hydroxylation of some pro and lys residues after their incorporation into
polypeptide chain as a most translational modification requiring molecular oxygen and vitamin c
and enzymes prolylhydroxylase and lysylhydroxylase respectively. The hydroxylysine residues
may also be enzymatically glycosylated.
Biosynthesis
, The polypeptide precursors of collagen molecule are formed in fibroblasts, osteoblasts and
chondroblasts and secreted into extracellular matrix. Like most proteins produced for export the
newly synthesized α chains of collagen contain signal sequence at N terminal ends which
facilitates the binding of ribosomes to rough endoplasmic reticulum and directs their passage into
RER where signal sequence is cleaved to yield pro α chain of collagen. After hydroxylation and
glycosylation pro α chain form procollagen. The formation of procollagen begins with
formation of interchain disulfide bonds between c-terminal extentions of pro α chain, bringing
the three chains into alignment favourable for helix formation. The rpocollagen molecules are
translocated to golgi where they are packaged into secretory vesicles which fuse with membrane
causing release of procollagen into extracellular space. Here they are cleaved by N and C
procollagen peptidases removing terminal propeptides releasing triple helical collagen
molecules.
The extracellular copper containg enzyme lysyl oxidase oxidatively deaminates some of lysly
and hydroxylys residues in collagen forming reactive aldehydes allysine and hydroxyallysine
which condense with neighbouring lys and hydroxylys residues of other collagen molecules
forming covalent cross links, essential for achieving high tensile strength.
Collagen diseases
Defects in any one of the steps involved in collagen synthesis results in diseases involving an
inability to form fibres properly. More than 1000 mutations have been detected in 22 genes
coding for twelve of collagen types.
1) Ehlers danlos syndrome ; heterogenous group of generalized connective tissues disorders
resulting from inheritable defects in metabolism of collagen. EDS can result from a
defiency of collagen processing enzymes like lysly hydroxylase or mutations in amino
acid sequences of collagen type I,II or IV. These patients have stretchy skins and loose
joints as in case Indian rubber man.
2) Osteogensis inperfecta; also known as brittle bone syndrome, is also a heterogenous
group of inherited disorders distinguished by bones that easily bend and fracture.
Retarded wound healing and humped back appearance are common features of this
diseses. Most patients have mutations in gene coding for pro 1 or pro 2 alpha chains of
type I collagen and the most common one is substitution of bulky side chain amino acid
for gly preventing proper folding of triple helix.
Elastin
Elastin is a connective tissue protein having rubber like properties. Elastic fibers of elastin are
composed of elastin and glucoprotein microfibrils are found in the lungs, walls of large arteries
and elastic ligaments. Elastin is a insoluble polymer synthesized from a precursor troelastin
which is a linear polypeptide of about 700 amino acids that are primarily small and nonpolar.
Elastin is rich in pro and lys but contains only a little hydroxypro and no hydroxylys.
Tropoelastin is secreted by the cell into extracellular space where it interacts with fibrillin which
acts as a scaffold onto which tropoelastin is deposited. Some of the lys side chains are
oxidatively deaminated by lysyl oxidase forming allysine, three of which plus one unaltered lys
side chain from same or neighbouring polypeptide forms a desmosine like cross link, which
produces elastin- an extensivel crosslinked rubbery network that can stretch bend in any
direction when stressed, giving connective tissues elasticity.
α-Keratin
The α-keratins have evolved for strength. Found in mammals, these proteins constitute almost
the entire dry weight of hair, wool, nails, claws, quills, horns, hooves, and much of the outer
