Lecture 16 - From Cells to Tissues Flashcards
What does the ECM consist of?
Proteins and proteoglycans.
Functions of the ECM?
- Inert scaffold - stabilise the physical structure of tissues.
- Define the cellular phenotype of cells residing within the ECM.
- Acts as a storage compartment for cell signalling factors.
4 major components of the ECM?
Collagens, proteoglycans, elastin and fibronectin.
What are collagens composed of?
Composed of alpha chains that wrap into a triple helix. These trimers can either be homo- or heteropolymers.
AA sequence?
In the AA sequence glycine is every 3rd residue. The 1st and 2nd AA are either proline, hydroxyproline or hydroxylysine.
Vitamin C is an essential cofactor of collagens. Why is it important? A lack of VC can cause what?
It hydrolyses proline and lysine residues. A lack of VC can result in scurvy.
Main structural role of collagen?
To provide tensile strength to tissues, e.g. bone.
Order of structure formation for collagen fibres?
Alpha chains –> triple helix –> collagen fibrils –> collagen fibres.
Why is glycine AA important for the structure of collagen?
It is small - enables the twisting of chains.
The family of collagens is large and diverse. Name some similarities and differences between the subgroups.
Collagen I - different alpha helices.
Collagen II - homotrimer.
Similarity - they both form trimers.
Steps of collagen synthesis?
- Synthesis of pro-alpha chains via ribosomes. They are called pro-alpha chains because they have propeptides at the N termnius.
- Hydroxylation step - OH residues added to the proline/lysine.
- Glycosylation of alpha chain.
- Assembly of 3 pro-alpha chains.
- Pro collagen triple helix is secreted into the extracellular space.
- Propeptides cleaved. Collagen helix produced. Fibril –> fibre.
Mutations in the alpha 1(I) and alpha 2 (I) genes cause what disease?
Osteogenesis imperfecta (OI). Brittle Bone disease. Bones break easily, blueing of the sclerae of the eye.
Dermatosparaxis (inherited disorder) shows what symptoms?
Causes fragile/loose/hyperflexible skin with bruising and bleeding. Causes by a mutation in the N-terminal propeptidase called ADAMTS-2, means that it cannot remove the propeptides in type I and III collagen.
What does a proteoglycan consist of?
Glucosaminoglycans (GAGs) covalently attached to a core protein (except hyaluronan).
Name the four classes of GAGs.
Hyaluronan (HA), chondroitin sulphate (CS), heparin sulphate (HS) and keratin sulphate (KS).