sakai- Fibrous Proteins Flashcards
Describe in general the composition of the ECM related to fibrous proteins (name two), specialized proteins and gel-forming group.
The general composition of the ECM consists of the fibrous proteins collagen and
elastin. Some specialized proteins are fibrillin, fibronectin, and laminin
The ECM contains also the gel-forming group of proteoglycans.
What are the amino acid composition, structure and function of collagen?
Collagen amino acid composition is characterized by glycine being one third of the amino acids and also by a high percentage of proline and lysine.
Collagen is an insoluble extracellular protein of the ECM. Collagen forms fibrils
or a mesh-like network.
One molecule of collagen, sometimes named tropocollagen, has a triple helical structure formed from three -chains tightly wound around each other.
Describe fibril-forming, network-forming and fibril associated collagens!
Fibril-forming collagens have a rope-like structure and function as supporting
proteins for examples in
Type I: skin, bone, and tendon, cornea
Type II: cartilage, inter-vertebral disk and vitreous body
Type III: blood vessels, and fetal skin
Network-forming collagens provide a three-dimensional mesh and function as
components of the basement membrane or beneath stratified squamous epithelia.
Fibril-associated collagens are found in cartilage and tendons and ligaments.
Do humans contain one, two or three genes for pro- chains of procollagen? How many pro- protein chains are used to form procollagen?
Humans contain two different genes for pro- chains for collagen synthesis.
Three pro- chains are used to form procollagen.
⦁ What is the function of propeptides in procollagen?
Propeptides on the carboxyl ends lock three pro- chains via disulfide bonds
together to allow the fast winding of the correct pro- chains around each other.
Propeptides on the N-terminals lock the formed triple helix together via disulfide
bonds which prevents unwinding of procollagen.
Propeptides are also necessary for the intracellular solubility of procollagen
⦁ What is procollagen, tropocollagen and collagen, respectively?
Procollagen is the soluble form inside of fibroblasts.
Tropocollagen is formed extracellular by enzymes from procollagen, it is insoluble after cleavage of the propeptides. Collagen is the assembly of several molecules of tropocollagens.
How is tropocollagen formed from procollagen?
Procollagen is cleaved to tropocollagen by cleavage of the N-terminal and the C-
terminal propeptides catalyzed by extracellular enzymes, procollagen peptidases.
⦁ Why does glycine represent about one third of amino acids in collagen?
Glycine has the smallest side chain of amino acids.
Three pro- chains are wound tightly around each other, which is possible when
glycine is in each third position as amino acid residue of one strand.
⦁ What is the advantage of the high proline content in collagen?
A prolyl residue leads to a bend in the polypeptide chain. These “kinks” facilitate
the tight winding of three chains around each other.
[this concept is also used when ropes for sailing are manufactured, like for sail
boats]
⦁ Why does vitamin C deficiency affect the stability of tropocollagen?
Vitamin C is needed for the formation of hydroxyproline residues that are able to
noncovalently stabilize the triple helix via many hydrogen bonds.
⦁ Which enzymes lack their coenzyme in vitamin C deficiency related to eventual collagen synthesis? Which products are normally formed and why are they important?
Vitamin C is needed as coenzyme for the intracellular enzymes prolyl hydroxylase
and lysyl hydroxylase in the fibroblasts during procollagen synthesis.
Hydroxyproline residues are needed in the collagen molecule for the stabilization
of the triple helix. They allow many hydrogen bonds between the strands
of the tightly wound triple helix..
Hydroxylysine residues reach out of the triple helix and they are not used to
stabilize the triple helix, but they can be glycosylated inside of fibroblasts.
In addition, hydroxylysine residues are used together with lysine residues for
eventual extracellular cross-linking of several collagen molecules. This cross-
linking is covalent and involves the extracellular enzyme lysyl oxidase.
⦁ What happens spontaneously extracellular? Is it the assembly of collagen fibrils or the formation of allysine residues? Which amino acid side chains are used for cross-linking?
The assembly of collagen fibrils happens spontaneously in the extracellular space.
The formation of allysine residues needs enzymatic catalysis by the extracellular
enzyme lysyl oxidase.
Lysyl oxidase oxidatively deaminates specific lysine or
hydroxylysine residues and the generated aldehyde groups can form covalent
links with the amino groups of neighboring lysine residues.
The cross-linking of collagen uses lysine, allysine and hydroxyallysine side
chains which form covalent bonds between collagen molecules.
⦁ Compare lysyl oxidase to lysyl hydroxylase!
Lysyl oxidase is extracellular and needs copper. This enzyme forms by deamination allysine or hydroxyallysine residues which are needed for cross-linking of collagen.
Lysyl hydroxylase is intracellular and needs vitamin C. This enzyme is needed
for formation of hydroxylysine residues in pro- chains.
⦁ Is the enzyme lysyl hydroxylase or is the enzyme lysyl oxidase needed for the eventual syntheses of both, collagen and elastin?
Lysyl oxidase is needed for the eventual synthesis of both, collagen and elastin.
A deficiency of lysyl oxidase or also of copper leads to defective cross-linking in
both, collagen and in elastin.
Lysyl hydroxylase is mainly needed for eventual collagen synthesis and nearly not
used for elastin synthesis. This is why a deficiency in vitamin C leads to
defective collagen synthesis but to mostly normal elastin synthesis.
⦁ Describe Ehlers-Danlos syndromes (EDS). What can be defective at the biochemical level? What are three general clinical manifestations in these syndromes?
Ehlers-Danlos syndromes is a heterogeneous group of disorders due to hereditary
defects of collagen synthesis.
The biochemical defect can be a mutation of the pro- chain gene, most clinically
important mutations are found in the gene for Type III collagen which can lead to
lethal vascular problems.
EDS can also result from deficiency of enzymes that are needed for collagen
synthesis, like prolyl hydroxylase, lysyl hydroxylase, lysyl oxidase or
procollagen peptidases.
The three general clinical manifestations are ⦁ Fragility of skin and vascular vessel walls (Type III collagen), can be lethal ⦁ Hypermobility of the joints (Type I collagen) ⦁ Stretchy skin, hyperextensibility (Type I collagen)
