FTM 44 - Fibrous Proteins Flashcards
What are the primay fibrous structural proteins of the ECM?
Collagen and Elastin
What are proteoglycans?
Protein strands with gel-forming sugars that are negatively charged
Broadly define what the ECM is and what it does.
A complext network of macromolecules that fills the spaces between cells and holds cells and tissue together and maintains the body’s three-dimensional structure.
What is the basement membrane essentially?
A sheet of ECM
Explain how the ECM is dynamic.
The ECM undergoes a constant remodeling by MMP (matrix metallo-proteinases) which include collagenases.
What affect does the ECM have on cellular processes?
How does the ECM protect against cancer and other microorganisms?
It prevents of limits their movements.
What can dysregulation of MMPs lead to?
The spread of cancer that was being kept in place
What is the most abundant fibrous protein and percentage of protein mass does it make up?
Collagen is the most abundant and it accounts for 25-30% of total body protein mass
How many different types of collagen have been characterized?
At least 28
Describe the basic structure of a collagen molecule.
A triple-helix of three protein α-chains which are tightly wound around each other to form a rigid rope-like structure.
How long is each collagen α-chain?
About 1,000 amino acids
Discuss the three most commonly found amino acids in collagen.
What is the purpose of the proline and hydroxyprline residues in collagen?
They provide kinks in the α-chain that allow for tight winding. Hydroxyproline residues also stabilize the triple helix by hydrogen bonding with glycine residues on othe other α-chains in the helix.
Discuss the important of lysine in collagen.
What sugars can lysine be glycosylated with in collagen?
Glucose and galactose
Collagen is fibril forming, network forming, and ________________.
Fibril-associated
What is the mnemonic for memorizing where each type of collagen is found
What are three common structural roles of collagen?
Why is Vitamin C important to collagen synthesis? What are some alternate names for vitamin C?
It is required by prolyl and lysyl hydrxylase to hydroxylate proline and lysine residues.
Vitamin C is also known as ascorbic acid and ascorbate
Why is iron important to collagen synthesis?
Same as Vitamin C, it is required by prolyl and lysyl hydroxylase to hydroxylate proline and lysine.
What causes scurvy and what are its symptoms?
Scurvy is caused by a Vitamin C deficiency leading to decreased staility and tensile strength of collagen.
Symptoms include bleeding gums, hemorrhages, and poor wound heeling
The biosynthesis of collagen begins at the level of ______ ___________.
Soluble procollagen.
What cells synthesize procollagen?
Fibroblasts, osteoblasts, and chondroblasts
How many different collage genes are there and how many of those are expressed? Name those genes and what they code for?
There are >40 collagen genes but only 2 are expressed: COL1A1 which codes for α1-chains and COL1A2 which codes for α2-chains.
What and how many α-chains are present in a collagen triple helix?
Two α1-chains and one α2-chain
What is tropocollagen? What does it do?
After procollagen is secreted by a cell its N-terminal and C-terminal propeptidases are cleaved by procollagen peptidases, producing tropocollagen.
Extracellular covalent cross-linking with lysine or modified lysine residues form mature collagen fibers.
List the 10 steps to the formation of type 1 collagen.
- COL1A1 and COL1A2 genes are transcribed.
- Translation occurs on RER into prepro-α chains that are fed into the RER lumen where the signal sequences will be removed forming pro-α chains.
- Selected pro and lys residues are hydroxylated.
- Hydroxylysine residues are O-glycosylated with glucose and galactose.
- Two α1 chains and one α2 chain assemble into a triple helix and intrachain and interchain disulfide bonds form at the unwound C-terminal end. Procollagen has been formed.
- Procollagen is packed into a transport vesicle and sent to the golgi
- The golgi then sends the procollagen into the ECM
- The N-terminal and C-termal unwound propeptides are cleaved by procollagen peptidases, producing tropocollagen.
- Tropocollagen spontaneously associates with other tropocollagen to form a collagen fibril (each overlaps its neighbor).
- Lysine and allysine residues of different α-chains covalently cross-link to form mature Type 1 collagen.
Why does a collagen triple helix always contain 2α1 and 1α2 chains. Why not 2α2 or 3α1/2?
For helix winding to begin the chains must be covalently linked at the carboxyl ends by disulfide bonds in specific way. This can only occur with 2α1 and 1α2 chains.
What prevents the procollagen helix from unwinding?
The cross linking of the N and C terminal chains
What keeps the procollagen molecule soluble in the cytosol?
The N and C terminal propeptides
How is the extracellular crosslinking of the tropocollagen molecules performed?
Why is copper important to collagen synthesis and what occurs if it is deficient?
Copper is required by lysyl oxidase to deaminate lysine. This allows for tropocollagen cross-linking to occur. Copper deficiency reduces collagen cross-linking.
What are the collagenopathies we need to know?
Ehlers-Danlos Syndrome
Osteogenesis Imperfecta
What is Ehlers-Danlos Syndrome and what can cause it?
What causes the classical form of Ehlers-Danlos syndrome and what are its symptoms?
What causes the vascular form of EDS and what are its symptoms?
What is Osteogenesis Imperfecta? What causes it? What is another name for OI? How many types of OI are there?
What is the mildest and most common type of OI? What is its scienticif name?
OI Type 1
Osteogenesis Imperfecta Tarda
What are the symptoms of OI Tarda (type 1)?
What is the most severe form of OI? What is its scientific name?
OI Type 2
Osteogenesis Imperfecta Congenita
What are the symptoms of OI type 2?
Things to know about OI types 3 and 4
OI type 3 is considered severe
OI type 4 is deforming but with normal sclerae
They can cause straight bones to develop bends, scoliosis, and dentiogenesis imperfecta.
Describe the basic structure and function of elastin.
Elastin has a high cross-linked insoluble amorphous (no clearly defined shape) structure. It is the major protein in elastic fibers which allow the flexibility in blood vessels, lungs, ligaments, and skin
What do we need to know about elastin synthesis?
What is unique about the way elastin cross-links? What is the result of this link?
How does elastin manage to reform after being stretched?
The hydrophobic effect
Elastin structure has alternating domains of hydrophilic sequences rich in lys and ala and hydrophobic sequences righ in gly, val, and pro.
Why the hydrophilic sequences of elastin rich in alanine?
Alanine is needed to separate the lysine residues from one another and it is small enough that it does not counteract the hydrophilicity of lysine.
Discuss the importance of lysine, hydroxyproline, and hydroxylysine in the cross-linking of elastin.
Lysein residues are used for cross-linking just like in collagen, however, hydroxyproline and hydroxylysine are rarely seen in elastin.
What is the elastinopathy we need to know? What causes it? How does it inherit?
Marfan Syndrome
It results from a autosomal dominant hereditary defect in the gene that encodes fibrillin-1, The gene for elastin is normal.
Over 300 mutations have been identified
What are the main characteristics of Marfan Syndrome?
Long limbs
Arachnodactyly (fingers and toes are abnormally long and slender)
Lens Dislocation
Aortic root dilation
Abnormal formation of rib cage
