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Lecture 4

Cell Physiology 3140A Lecture 4.docx

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Department
Physiology
Course
Physiology 3140A
Professor
Anita Woods
Semester
Fall

Description
Cell Physiology 3140A Lecture 4 September 16, 2013 Cell Physiology – Cell Matrix Interactions II Collagen Structure - 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 together. - 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 removed. 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). Collagen Categorizations -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
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