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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | FIBROUS PROTEIN | NOTED BY FAKHRY (IG @SFAKHRYM)
v Overview
o Each fibrous protein exhibits special mechanical properties, resulting from its unique structure, which are obtained by combining specific
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amino acids into regular, secondary structural elements;
Contrast to globular proteins, whose shapes are the result of complex interactions between secondary, tertiary, and, sometimes,
quaternary structural elements
Fibrous vs Globular protein
• Fibrous proteins are generally composed of long and narrow strands and have a structural unit role [the are something] | Globular
proteins generally have a more compact and rounded shape and have functional roles [they do something]

Fibrous protein have some similar properties to each other:
• They contain long polypeptide chains with repeating sequences of amino acids
• The amino acids have non-polar R groups so the proteins are insoluble in water
• The polypeptide chains are able to form fibers which make the protein stronger

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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | FIBROUS PROTEIN | NOTED BY FAKHRY (IG @SFAKHRYM)
v Collagen
• It is the most abundant protein in the human body
• The typical is a long, rigid structure in which three polypeptide (referred to as α chains) are wound around one another in a rope-like triple
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helix
Although these molecules are found throughout the body, their types and organization are dictated by the structural role collagen plays in a
particular organ
Types (see figure 4
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44)

The collagen superfamily of proteins includes more than 25 collagen types as well as additional proteins that have collagen-like domains
The three polypeptide α-chains are held together by interchain hydrogen bonds

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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | FIBROUS PROTEIN | NOTED BY FAKHRY (IG @SFAKHRYM)
Variations in the amino acid sequence of the α-chains result in structural components that are about the same size (approximately 1000
amino acids long) but with slightly different properties
§ These α-chains are combined to form the various types of collagens found in the tissues
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Fibril-forming collagens (have rope-like structure; in electron microscope, these linear polymers of fibrils have characteristic banding patterns,
reflecting the regular staggered packing of the individual collagen molecules in the fibril)
§ Type I, II, and III are the fibrillar collagens and have the rope-like structure described above for a typical collagen molecule
§ Type I collagen fibers are found in supporting elements in high tensile strength (e
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, tendon and cornea)
§ Type II collagen molecules are restricted to cartilaginous structure
§ Type III collagen are prevalent in more distensible tissues such as blood vessels
Network-forming collagens
§ Types IV and VIII form a three-dimensional mesh, rather than distinct fibrils
• Example: type IV molecules assemble into a sheet or meshwork that constitutes a major part of basement membranes
Fibril-associated collagens
§ Type IX and XII bind to the surface off collagen fibrils, linking these fibrils to one another and to other components in the ECM
Structure
• Amino acid sequence
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Collagen is rich in proline and glycine (both are important in the formation of the triple-stranded helix)
• Prolines facilitates the formation of the helical conformation of each α-chain, because its ring structure causes "kinks" in
the peptide chain
• The presence of proline dictates that the helical conformation of the α-chain cannot be an α helix
• Glycine, it is found in every third position of the polypeptide chain;
• It fits into the restricted spaces where the three chains of the helix come together
• The glycine residues are part of a repeating sequence, -Gly-X-Y-, where X is frequently proline, and Y is often
hydroxyproline (but can be hydroxylysine)
• Thus, most of the α-chain can be regarded as polypeptide whose sequence can be represented as (-Gly-Pro-Hyp-)333
• Triple-helical structure
§ It is a fibrous protein that has an elongated, triple-helical structure that is stabilized by interchain hydrogen bonds
Hydroxyproline and hydroxylysine
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§ Collagen contain hydroxyproline and hydroxylysine, which are not present in most other proteins
§ These residues result from the hydroxylation of some of the proline and lysine residues after their incorporation into polypeptide
chains
• The hydroxylation is, thus, an example of posttranslational modification
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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | FIBROUS PROTEIN | NOTED BY FAKHRY (IG @SFAKHRYM)
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Generation of hydroxyproline maximizes formation of interchain hydrogen bonds that stabilize the triple-helical structure

Glycosylation
§ The hydroxyl group of the hydroxylysine residues of collagen may be enzymatically glycosylated
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• The signal sequence facilitates the binding of ribosome to the RER, and directs the passage of the prepro-α chain into the
lumen of the RER
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Additionally, collagen fibrils cannot be cross-linked, greatly
decreasing the tensile strength of the assembled fiber - SCURVY
Without the hydroxylating enzyme, prolyl hydroxylase and lysyl hydroxylase, are unable to function
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• Glycosylation
§ Some hydroxylysine residues are modified by glycosylation with glucose or glycosyl-galactose
Assembly
and secretion
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§ After hydroxylation and glycosylation, the three pro-α chains form procollagen, a precursor of collagen that has a central region of
triple helix flanked by the nonhelical amino- and carboxy-terminal extensions called propeptides
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BIOCHEMISTRY | PROTEIN STRUCTURE AND FUNCTION | FIBROUS PROTEIN | NOTED BY FAKHRY (IG @SFAKHRYM)
The formation of procollagen begins with formation of interchain disulfide bonds between the C-terminal extensions of the pro-αchains
• This bring the three α-chains into an alignment favorable for helix formation
§ The procollagen molecules move through the Golgi apparatus, where they are packaged in secretory vesicles
• The vesicles fuse with the cell membrane, causing the release of procollagen molecules into the extracellular space
Extracellular cleavage of procollagen molecules
§ After their release, the procollagen molecules are cleaved by N- and C- procollagen peptides, which remove the terminal
propeptides, releasing triple-helical tropocollagen molecules
Formation of collagen fibrils
§ Tropocollagen molecules spontaneously associate to form collagen fibrils
Cross-link formation
§ The fibrillar array of collagen molecules serves as a substrate for lysyl oxidase
Lysyl oxidase one of several copper containing enzymes
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• Disruption in copper homeostasis causes copper dificiency (X-linked Menkes disease) or overload (Wilson disease)
Degradation
§ Breakdown of collagen fibers is dependent of the proteolytic action of collagenases, which are part of a large family of matrix
metalloproteinases
• For type I collagen, the cleavage site is specific, generating three-quarter and one-quarter length fragments
• These fragments are further degraded by other matrix proteinases
Collagen diseases
§ Ehlers-Danlos Syndrome (EDS)
• It is a heterogenous group of connective tissue disorders that result from inheritable defects in the metabolism of fibrillar
collagen molecules
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Type I OI is the most common form, is characterized by mild bone fragility, hearing loss, and blue sclera
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§ The proteolytic activity of elastase can destroy the elastin in alveolar walls in unopposed by the action of ATT --> Emphysema
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v Insulin
o Structure of Insulin
• Insulin is a polypeptide hormone that is produced by the β cells of the pancreas; It has 51 amino acids in two polypeptide chains,
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which are linked by two disulfide bridges
Synthesis of insulin
• Preproinsulin is synthesized on the rough endoplasmic reticulum and the pre (signal) sequence is removed to form proinsulin
• In secretory granules, proinsulin is cleaved, and the C-peptide is released

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