Biochemistry Fibrous Proteins PDF - Saint Louis University SOM 2028

SAINT LOUIS UNIVERSITY P.08 Fibrous Proteins Dr. Yasay | SEPTEMBER 04, 2024...

SAINT LOUIS UNIVERSITY P.08 Fibrous Proteins Dr. Yasay | SEPTEMBER 04, 2024 SOM 2028 OUTLINE Collagen and elastin are the common examples of well- characterized fibrous proteins of the extracellular matrix (ECM). I. OVERVIEW OF FIBROUS PROTEINS …………………..…….1 Collagen and elastin can be found as components of the skin, II. COLLAGEN ………………..………………………………….….1 connective tissue, blood vessel walls, and the sclera and cornea A. TYPES OF COLLAGEN …………...................................2 of the eye. 1. FIBRIL-FORMING COLLAGENS …….……………… 2 o Aging: ↓ collagen and elastin = skin sags 2. NETWORK-FORMING COLLAGENS …..……………2 3. FIBRIL-ASSOCIATED COLLAGENS ………………...3 B. STRUCTURE 1. AMINO ACID SEQUENCE …………………………….3 2. HYDROXYLATION ………………………...…………...3 3. GLYCOSYLATION ……………………………………...3 III. CHECKPOINT ………………………...…………...4 IV. REFERENCES……….…………………………….4 I. OVERVIEW OF FIBROUS PROTEINS Protein with elongated shape Provide structural support for cells and tissues These are special types of helices present n two fibrous proteins alpha-keratin and collagen. Figure 2. Comparison between younger and older skin. These proteins form long fibers that sere a structural role in the human body II. COLLAGEN ○ Triple helix: right sided The most abundant protein in the human body. ○ Alpha helix: left sided The collagen superfamily of proteins includes more than 25 ○ Gap areas: striated appearance collagen types as well as additional proteins that have collagen- Each fibrous protein exhibits special mechanical properties, like domains. resulting from its unique structure. Made up of a long, rigid structure of three polypeptides (called α- Their unique structure is obtained by combining specific amino chains) wound around one another in a rope-like triple helix. acids into regular, secondary structural elements. The three polypeptide α chains are held together by an interchain of hydrogen bonds. Figure 3. Collagen Structure These α-chains are combined to form the various types of collagens found in the tissues. Their types and organization are dictated by the structural role collagen plays in a particular organ. Figure 1. Collagen and Elastin Structures Types and Organization of Collagen o Dispersed - gel-like, gives support to the structure. E.g. Vitreous humor in the eye and extracellular matrix o LIM, SAQUING, JUGUILON, MARTIN, ALARCIO Page 1 of 4  SAINT LOUIS UNIVERSITY P.08 Fibrous Proteins Dr. Yasay | SEPTEMBER 04, 2024 SOM 2028 Under electron microscope, these have a banding characteristic, o Stacked – collagen fibers can be stacked, as to transmit light with where it reflects the regular staggered packing of the individual a minimum amount of scattering. collagen molecules in the fibril. E.g. Cornea of the eye ○ TYPE 1 COLLAGEN - most common type, contains two alpha I chains and one alpha II chain. - composed of collagen fibrils that are found in supporting elements of high tensile strength - ex. tendons and corneas ○ TYPE II COLLAGEN - contains three alpha I chains - restricted to the cartilaginous structures. - ex. cartilage, bone, intervertebral disc, vitreous body ○ TYPE III COLLAGEN - fibers derived from type III collagen are prevalent in Figure 4. Cornea and Vitreous humor. more distensible tissues such as blood vessels. - ex. blood vessel, skin, muscle o Bundled in light parallel fibers - fibrous structures will provide great tensile strength in the area. E.g. Tendons o Right Angle with each other – which can resist high mechanical shear. E.g. Bone Figure 7. Fibril-forming collagen structure. 2. NETWORK-FORMING COLLAGENS Figure 5. Tendon and Bone. Types IV and VIII form a three-dimensional mesh, rather than A. TYPES OF COLLAGEN distinct fibrils. Variations in the amino acid sequence results into structural For example, type IV molecules assemble into a sheet or components that have different properties. meshwork that constitute a major part of the basement Difference in their function comes from the fact that there are different types of chains that compose collagen fibers that also membranes. dictate their function or their role. o TYPE IV - ex. basement membrane Figure 8. Basement Membrane Figure 6. Types of Collagen with their tissue distribution. 1. FIBRIL-FORMING COLLAGENS Types I, II, and III are the fibrillar collagens and have rope-like structure. LIM, SAQUING, JUGUILON, MARTIN, ALARCIO Page 2 of 4  SAINT LOUIS UNIVERSITY P.08 Fibrous Proteins Dr. Yasay | SEPTEMBER 04, 2024 SOM 2028 Figure 9. Electron micrograph of polygonal network formed by - Prolyl hydroxylase will not function if there is no iron association of collagen type IV monomers in its reduced state o TYPE VIII - The structure is good when the collagen is taut. - ex. corneal and vascular endothelium 3. FIBRIL-ASSOCIATED COLLAGENS Types IX and XII bind to the surface of collagen fibrils, linking these to one another and to other components in the ECM. o TYPE IX - ex. cartilage o TYPE XII - ex. tendon, ligament, some other tissues A. STRUCTURE OF COLLAGEN Has an elongated, triple-helical structure that is stabilized by an interchain of hydrogen bonds. Collagen is a fibrous protein, unlike globular proteins that are folded into compact structures. AMINO ACID SEQUENCE Collagen is rich in proline and glycine, both of which are important in the formation of the triple-stranded helix. Figure 11. Hydroxylation of proline residues in pro-a chains of collagen Sequence can be represented as glycine, proline and by prolyl hydroxylase. [Note: Fe2+ (hydroxylase cofactor) is protected from hydroxyproline or hydroxy lysine. oxidation to Fe3+ by ascorbate (vitamin C).] o PROLINE - facilitates the formation of the helical conformation of each alpha Why is Ascorbic acid important? chain because its ring structure causes “kinks” in the peptide chain. Not enough ascorbic acid in the diet causes improper hydrogen These kinks manifest as the helical areas. Thus, it's not bonds. So, the structure is not stabilized or collagen becomes straight because proline is most likely found in areas less taut. Which is presented by falling teeth, blood vessels that where a kink or convolution is seen. easily break. o GLYCINE - it’s the smallest amino acid, and is found in every third position GLYCOSYLATION of the polypeptide chain. The hydroxyl group of the hydroxylysine residues of collagen may It fits into the restricted spaces where the three chains be enzymatically glycosylated. of the helix come together. Most commonly, glucose and galactose are sequentially glycine residues are part of the repeating sequence, - attached to the polypeptide chain prior to triple-helix formation. Gly-X-Y-, where X is usually proline, and Y is often hydroxyproline. o HYDROXYLYSINE and HYDROXYPROLINE called as nonstandard amino acids (not present in most other proteins) resulted from hydroxylation. Figure 10. Amino acid sequence of a portion of the αlpha-1 chain of collagen. Hyp = hydroxyproline; Hyl = hydroxylysine HYDROXYLATION Hydroxylation is a post-translational modification. Interchain hydrogen bonds in between the three chains is maximized with the presence of hydroxyproline; thus, stabilizing the collagen structure Proline residue in pro-alpha chains is eventually hydroxylated by proline hydroxylase, forming hydroxyproline residue. Other substances needed: o Prolyl hydroxylase or Lysine hydroxylase - enzyme responsible for the hydroxylation of proline residue o Iron in ferrous state o Ascorbic acid or ascorbate (Vitamin C) - Cofactor of prolyl: prevents the oxidation of ferrous ion into ferric ion LIM, SAQUING, JUGUILON, MARTIN, ALARCIO Page 3 of 4  SAINT LOUIS UNIVERSITY P.08 Fibrous Proteins Dr. Yasay | SEPTEMBER 04, 2024 SOM 2028 III. CHECKPOINT! 1. True / False: Collagen is an amino acid peptide, is made up of amino acid peptide sequences? 2. True / False: Collagen molecule is made up of three alpha helices? 3. True / False: The alpha strand of collagen is a helix? 4. This type of collagen is found in tendon 5. What type of proteins have an elongated shape and provide structural support for cells and tissues? 6. What are the two fibrous proteins that contain special helices? 7. What mechanical property results from the unique structure of fibrous proteins? 8. Which fibrous proteins are common examples found in the extracellular matrix (ECM) and where can they be found in the human body? 9. What type of collagen forms a three-dimensional mesh and is found in the basement membrane? Type IV collagen 9. blood vessel walls, sclera, and cornea of the eye Collagen and elastin; found in skin, connective tissue, 8. Structural/mechanical support 7. Alpha-keratin and collagen 6. Fibrous proteins 5. Firbril forming and Network Forming 4. True 3. True 2. True 1. IV. REFERENCES Ferrier, D. (2017). Lippincott Illustrated Reviews: Biochemistry (7th Edition). Philadelphia, PA: Wolters Kluwer Health. LIM, SAQUING, JUGUILON, MARTIN, ALARCIO Page 4 of 4