Cell Physiology 3140A
September 16, 2013
Cell Physiology – Cell Matrix Interactions II
- Collagen is the most abundant component in the ECM. The picture below is a
collagen fibril. There is an alpha helix and we have 3 of them to form a trimer. 3
alpha helical polypeptides, these 3 things will wind together to form the collagen
fibril. The amino acids that sit in the middle of the alpha helix that wraps around
itself are the small amino acids, glycine. Glycine is a small amino acid that allows for
no external subunits sticking out. It doesn’t get in the way of he alpha helix forming.
There are 2 other amino acids that repeats and it is usually proline and
hydroyproline. They wrap around together to form a trimeric alpha helix. In the
collagen polypeptide there is a globular N domain and a C domain. Both termini
have a globular domain (not a helix). When the polypeptides are made the globular
domain exist. We need those domains to help wind the alpha helix, or the trimer
- There are 20+ different types of collagen (20 different types in the proteome).
Collagen has 3 polypeptides, so all 3 polypeptides together creates 1 collagen. These
polypeptide chains can all come from the same gene to make it a homotrimer or
from different genes to make a heterotrimer. In the human genome, there are 34
genes that will result in a polypeptide chain that will contribute to the final collagen
fibrils. There are 20 different collagen fibrils and around 34 genes that make those
individual polypeptide chains. - Collagen types I, II, III (Typical Collagens): These polypeptide chains are
translated in ER. These polypeptide chains have to be post-translationally modified.
The types of post-translation are hydroxylation (remove H to add OH) and
glycosylation. Specifically the amino acids that that are hydroxylated are proline
and lysine. Enzymes are going to look for prolines and lysines that look for specific
sequences before and after the amino acids. Scurvy is a disease that breaks down
collagen. Enzymes that hydroxylate the polypeptides need vitamin C. Without that,
collagen can’t be formed. If you hydroxylate the polypeptide properly, then we can
form the multimer or the collagen fibril (triple helix and globular domains). This
collagen then goes through the golgi apparatus where an oligosaccharide (multiple
sugars) is added to the fibrils. The collagen fibrils are then secreted to the
surroundings where the N and C domains are cut off. Crosslinking occurs and there
is an external enzyme found outside of the cells that will modify further these fibrils
and allow for crosslinking to form bigger fibers of collagen, or tropocollagen.
- Collagen type IV: There is no triple helix formation. The polypeptides are
glycosylated and hydroxylated. They form a dimer first, then dimers join dimers to
form a quaternary , 4 polypeptide wounded shape. This multimer is excreted goes
through addition of oligosaccharides. They do not remove the globular domains.
The N terminal and C terminal are not removed and they are a component of the
multimer, or tropocollagen fiber. -Collagen types X, VIII: Triple helix is formed but N and C domains are not
Differences Between Collagen Types
- There are a # of different helix repeats, ie length of the triple helix portion. The
glycine, X and Y can repeat 40 times or a 100 times. That central alpha helix that
forms that trimer can be short or be fairly long. The length of the triple helix portion
varies in the collagen types. When collagen as a heterotrimer, polypeptides that
come from different genes, they all have the same number of helical repeats. They
perfectly connect together in that triple helical repeats. It’s the variation between
the collagen types (ex. Collagen type I is different then collagen type II alpha helix).
- There are a # of interrupting segments within the helix. This means that an
amino acid that is not a glycine in the center or X or Y. This creates a bulge or bump
in the helix. Not all alpha helices are glycine, X, Y perfectly along their length. Many
of them has many interrupting portions to their alpha helix. This is important
because when 2 collagen fibrils cross together, there are a lot of bumps in the alpha
helix and it will not bind as tightly. The more interruptions, the less tightly alpha
helices from different collagens can interact with each other.
- The shape of globular C and N domains contributes to differences. Shape and
size, some have larger C domains and smaller N domains. They are not the same for
each collagen molecule.
- There are differences in covalent modification of triple helix. Amino acid
sequence of the polypeptide determines the molecules added to the chain. (Ex.
Oligosaccharides, hydroxylation, aldehydes). Example, more lysine would contribute
to more hydroxyl groups added (more post-translational modification).
-1) Fibrillar Collagens: This collagen is the most abundant in the body. They
aggregate into fibers that are very organized. It is good that they organize in this
fashion is because they provide the mechanical support of the body. Ex. Bones,
tendons, teeth. These structures have fibrillar collagens as part of their components
or ECM. They are the support collagens of the body.
- 2) Sheet-forming Collagens: These types of collagen form sheets. It is a 2D
network of collagen. These are thin sheets or collagen that are not organized side by
side. Typical tissues in the body that is made up of a lot of this collagen are basal
lamina. Basal laminas are those anchor tissues, or epithelial cells. They are cells that
sit together closely and they are anchored by these collagens. These collagens are
important for strength, mostly between cells closely packed together. These
collagens are also important for filtration throughout the body. Kidneys have
collagen to filtrate blood. Capillaries have basal lamina that allows some motion
between blood and fluid. So these collagens are like a sift and a structural supporter. -3) Fibril-Associated Collagens: These are collagens that associate with the
Fibrillar type collagens. Fibrillar collagens line up nicely together, Fibrillar-
associated collagens kind of stick collagens to each other, using a collagen as a
bridge. They associate with other Fibrillar collagens linking these collagens
together and linking them to other components of the ECM (proteoglycans).
-4) Transmembrane Collagens: Least abundant collagen. This collagen breaks the
rules of collagens that it passes through the cell membrane. We have a collagen
molecule that is kind of embedded within the cell, transverses through the
membrane and it sticks out into the matrix and associates with other collagens. It
acts as an anchoring protein, extracellular matrix component and a receptor (giving
info to cell from ECM).
Collagen Expression Patterns
- Chart in workbook
-Type I: The structural feature is fibrillar and heterotrimeric. It is expressed in skin,
bones and ligaments. The collagen in bone is different from collagen in skin. The
skin is stretchable but the bones are not. This is due to with the other proteins in the
ECM and how much of it is pre