Biochemistry: Fibrous Proteins Overview

Biochemistry Study Notes

• Sheet number: 20
• Document Year: 2024
• Written by: Duha Alnader & Wedad Mustafa
• Edited by: Reem Ghnemat
• Doctor: Dr. NafezaButarboush

Fibrous Proteins

• Structure-Function Relationship: Fibrous proteins have a strong, solid structure for support. They have a specific type of secondary structure that repeats, allowing for compression and expulsion of water, creating a strong structure. They may also have tertiary and quaternary structures.
• Biological Functions: Enzymes catalyze reactions. Transport molecules include hemoglobin and lipoproteins. Contractile proteins like myosin and actin, along with structural proteins such as collagen and keratin, are involved in movement and structure. Defense proteins include antibodies (i.e. immunoglobulins). Signaling molecules like hormones are involved in communication, along with receptors and toxins (e.g., diphtheria & enterotoxins).
• Types: Fibrous proteins have a uniform secondary structure only. Globular proteins have three-dimensional compact structures.
• Examples: Collagen, elastin, and keratin are fibrous proteins. Myoglobin, hemoglobin, and immunoglobulins are globular proteins.

Extracellular Matrix

• Composition: The extracellular space is filled with an intricate network of macromolecules including proteins and polysaccharides. Collagen is synthesized by cells and released into the extracellular fluid (ECF), providing structural support and tissue straightening.
• Collagen Properties: Collagen accounts for 40% of proteins in the body. It is a family of fibrous proteins with 25 types found in all multicellular animals. Type I collagen is the most common, found in bones and cartilages. Types differ in amino acid composition but share similar structural features. The main function of collagen is to provide structural support in tissues. It is stiff.
• Structure of Collagen: It is a left-handed, triple-stranded, helical protein (tropocollagen). The collagen helix is more extended than the typical α-helix. Every 3 amino acids, a glycine is present. Glycine is the most frequent amino acid in collagen and breaks up the α-helix. Collagen has high amounts of glycine (33%), and proline (13%), and hydroxyproline (9%) & hydroxylysine.

Structure of Collagen

• Properties: Left-handed, triple-stranded, helical protein where three polypeptide chains (a-chains) are wound around one another. Compared to α-helices, collagen helices are more extended (3.3 residues per turn). The basic unit is tropocollagen. Glycine (a breaker of alpha-helices) is present every 3rd amino acid in the sequence. Collagen differs in length (5.4A) and number of amino acids per turn (3.6A) from α-helices.
• Composition: Rich in glycine (33%), proline (13%) and hydroxyproline (9%). The modified form of proline is hydroxyproline, which creates kinks that disrupt the helical structure.

Functional purpose of amino acids:

• Glycine: Packs the three α-chains together to form the final collagen superhelix. It causes the formation of the final triple helical structure.
• Proline: Creates kinks and stabilizes the helical conformation of each α chain.

Hydroxylysine (modified Lysine)

• Lysine can form an aldehyde, or remain as is.
• Hydroxylysine acts as an attachment site for polysaccharides, making the polypeptide chain a glycoprotein
• Two enzymes hydroxylase and oxidase are involved in forming modified forms (crosslinks) of lysine.

Oxidation of lysine

• Some lysines are oxidized to aldehyde (allysine)
• Covalent aldol linkages form between hydroxylysines or other modified lysines creating covalent bonds between polypeptide chains.

Function of Cross-Linking

• Purpose: Cross-linking strengthens collagen fibers.
• Formation: The formation of cross-linking in collagen involves the modification of lysine residues. Hydroxylysine is first formed and then converted to an aldehyde (oxidation). This covalent bond formation stabilizes the side-by-side packing of collagen molecules, creating stronger fibers.

Formation of collagen fibers

• Following release of procollagen, 5 molecules connect through aldehyde bonds to form microfibrils.

• Microfibrils combine forming larger collagen fibers which are stabilized by cross-links between lysine residues

Scurvy (acquired disease):

• Cause: A dietary deficiency of vitamin C (ascorbic acid).
• Mechanism: Vitamin C is a coenzyme that is necessary for the proper hydroxylation of proline and lysine residues in collagen. Without this hydroxylation process, the triple helix structure of collagen cannot form. Defective collagen is rapidly degraded.
• Symptoms: Blood vessel fragility, spontaneous bleeding, bruising, and teeth loosening.

Elastins

• Properties: Prevents tearing of tissues during stretching. Has weak bonds between small polypeptides and primarily non-polar interactions.
• Resilience vs. Flexibility: Important for tissues requiring both strength and elasticity, like skin, blood vessels, and lungs. Requires elasticity for recoil from stretching.
• Composition: Rich in proline, glycine, and lysine. Has allysine but a lack of lysyl hydroxylase. Non-glycosylated.
• Cross-linking: Cross-links occur between allysine residues.
• Structure: Two segment types alternate along the chain: hydrophobic segments for elasticity, and alanine/lysine rich helical segments.

Keratins

• Structure: Unusual content of cysteine (forming disulfide bonds), is found in nails, hair, horns, and skin. α-keratin tends to have higher cysteine content/disulfide bonds, leading to greater hardness.
• α-Keratin: The protein of hair, fingernails, and animal skin. Has high cysteine content. Right-handed α-helix.
• Structure: Repeated amino acid sequences and biological functions.
• Cross-linking: Three allysine and one unaltered lysyl side chains form desmosine.

Keratins structure

• Types of Keratin: Two types α-helix and β-sheet.
• Structure: Helical arrangement. Protofibrils, microfibrils, and macrofibrils. Disulfide bonds between keratin molecules make keratin stronger.
• Hardening: Disulfide cross-links in keratin can be hardened further.

Hair design

• Temporary wave: Water molecules weaken the hydrogen bonds in the hair, allowing it to be shaped.
• Permanent wave: A reducing substance breaks the disulfide bonds, allowing the hair to be reshaped. An oxidizing agent then reforms the bonds in the new position.

Explore the essential aspects of fibrous proteins in this biochemistry quiz. Understand their structure-function relationship, biological roles, and various types. This quiz is based on study notes that provide deeper insights into the fascinating world of fibrous proteins.