1. Fibrous proteins
ELASTIN

2. Major fibrous protein of epithelial tissues is
a keratin
Major fibrous proteins of connective tissue are:
Collagen and Elastin
Much or most of the polypeptide chain is parallel to a single axis
Fibrous proteins are often mechanically strong & highly cross-linked
Fibrous proteins are usually insoluble
Usually play a structural role

3. ELASTIN
It is a connective tissue protein that is responsible for properties of extensibiity and elastic recoil in tissues. Elastin is present in large amounts, particularly in tissues that require these physical properties e.g. lung, blood vessels and elastic ligaments and small amounts in ear and skin.

4. Elastin: Where: elastic connective tissues.
Cellular location: extracellular matrix
Function: add elasticity to connective tissue
Structure: beta spiral
Crosslink: desmosine

5. Some of the lysyl side chains of the tropoelastin polypeptides are oxidatively deaminated by lysyl oxidase, forming allysine residues. Three of the allysyl side chains plus one unaltered lysyl side chain from the same or neighboring polypeptides form a desmosine cross-link .THIS PRODUCES ELASTIN—an extensively interconnected, rubbery network that can stretch and bend in any direction when stressed, giving connective tissue elasticity

7. In contrast to collagen, which forms fibers that are tough and have high tensile strength, elastin is a connective tissue protein with rubber-like properties. Elastic fibers are composed of elastin and glycoprotein microfibrils. They can be stretched to several times their normal length, but recoil to their original shape when the stretching force is relaxed.

8. STRUCTURE OF ELASTIN
Elastin is an insoluble protein polymer synthesized from a precursor, TROPOELASTIN, which is a linear polypeptide composed of about 700 amino acids that are primarily small and nonpolar (for example, glycine, alanine, and valine).
Tropoelastin is secreted by the cell into the extracellular space. There it interacts with specific glycoprotein microfibrils, such as FIBRILLIN, which function as a scaffold onto which tropoelastin is deposited.
Elastin is also rich in proline and lysine, but contains only a little hydroxyproline and hydroxylysine.

9. FIBRILLIN
. A large glycoprotein (about 350 KDa) that is a structural component of microfibrils nm fibers found in many tissues. It is secreted into ECM by fibroblast and becomes incorporated into the insoluble microfibrils which appear to provide a scaffold for deposition of elastin.
Genetic defects in fibrillin result in Marfan’s Syndrome, characterized by a tall gaunt appearance, joint problems, an often leading to death by aortic aneurysm.

10. Fibrillin Where: connective tissue; extracellular matrix
Structure: forms outer envelope of elastin microfibrils

11. DYNAMIC STRUCTURE OF ELASTIN:
The structure of elastin is called a b spiral, and is loosely held together by the hydrophobic force.
It is easily deformed to an extended configuration, but will relax back to a compact conformation.
In support of chapter 8, pg. 10
From Li B, and Daggett V. Molecular basis for the extensibility of elastin. J. Muscle Res. and Cell Motility 23: (2003).
Repeating unit: PGVGV

13. ELASTIC FIBERS. These scanning electron micrographs show (A) a low-power view of a segment of a dog's aorta and (B) a high-power view of the dense network of longitudinally oriented elastic fibers in the outer layer of the same blood vessel. All the other components have been digested away with enzymes and formic acid.

14. MARFAN SYNDROME.
It is a relatively prevalent inherited disease affecting connective tissues. It is inherited as an autosomal dominant trait. It affects the eyes, the skeletal system and hyper-extensibility of the joints and cardiovascular system. This syndrome is due to mutations in the gene for fibrilin.
With this disease, abnormal fibrillin protein is incorporated into microfibrils along with normal fibrillin, inhibiting the formation of functional microfibrils. [Note: Patients with OI, EDS, or Marfan syndrome may have blue sclera due to tissue thinning that allows underlying pigment to show through.]

15. Abraham Lincoln is thought to have had Marfan’s syndrome.
Image from Wikipedia.

16. CT reconstruction of an aortic aneurysm.
The Figure is from Wikipedia.

17. Deletion of elastin gene have been found in 90% of the subjects with Williams syndrome, a developmental disorder affecting connective tissue and the central nervous system. A number of skin diseases are associated with accumulation of elastin. Alternatively, a decrease of elastin is found in conditions such as pulmonary emphysema and aging of the skin

18. Genetic defects in elastin underlie Williams Syndrome
Facial features associated with Williams Syndrome
Dental features include small widely spaced teeth and malocclusion.
In support of chapter 8, pg. 10.
From Morris CA, and Mervis CB. Williams Syndrome and related disorders. Ann. Rev. Genomics Hum. Genet. 1: (2000).

19. á1-Antitrypsin: Blood and other body fluids contain a protein, á1-antitrypsin (á1-AT, A1AT, currently also called á1-antiproteinase), that inhibits a number of proteolytic enzymes (also called proteases or proteinases) that hydrolyze and destroy proteins.
á1-AT has the important physiologic role of inhibiting neutrophil elastase––a powerful protease that is released into the extracellular space, and degrades elastin of alveolar walls, as well as other structural proteins in a variety of tissues . Most of the á1-AT found in plasma is synthesized and secreted by the liver. The remainder is synthesized by several tissues, including monocytes and alveolar macrophages, which may be important in the prevention of local tissue injury by elastase

20. Role of á1-AT in the lungs:
In the normal lung, the alveoli are chronically exposed to low levels of neutrophil elastase released from activated and degenerating neutrophils. This proteolytic activity can destroy the elastin in alveolar walls if unopposed by the action of á1-AT, the most important inhibitor of neutrophil elastase. Because lung tissue cannot regenerate, emphysema results from the destruction of the connective tissue of alveolar walls.

21. á1-Antitrypsin deficiency (summary)
In the alveoli, elastase released by activated and degenerating neutrophils is normally inhibited by á1 -antitrypsin.
Genetic defects in á1-antitrypsin can lead to emphysema and cirrhosis.
Smoking increases risk.
The deficiency of elastase inhibitor can be reversed by weekly intravenous administration of á1 -AT.