Fibrous proteins


Published on

  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Fibrous proteins

  1. 1. COLLAGEN and ELASTIN are examples of well characterized fibrous proteins that serve structural functions in the body.Each fibrous protein exbits special mechanical properties,resulting from its unique structure,which are obtained by combing specific amino acids into regular,secondary structural elements.
  2. 2. COLLAGENCOLLAGEN is the most abundant protein in the human body.A typical collagen molecule is a long, rigid structure in which three polypeptides(referred to as α-chains) are wound around one another in a rope like triple helix.
  3. 3. Types of CollagenThe collagen superfamily of proteins include more than twenty collagen types,as well as additional proteins that have collagen like properties.The three polypeptide chains are held together by hydrogen bonds between the chains.Variations in the aminoacid sequence of the α chains result in structural components that are about the same size(approximately 100 aminoacids long),but with slightly different properties.
  4. 4. The α chains are combined to form various types of collagen found in the tissues.For example Type 1 collagen contains two α1 chains and one α2 chain (α1 ₂ α2 ).Type 2 collagen contains three α1(α1 ₃) chain.The collagens can be organized into three groups depending upon their location and functions in the body.
  5. 5. Structure of collagenAmino acid sequence1.Rich in proline and glycine.2. –Gly-X-Y-3.X is frequently PROLINE and Y is Hydroxyproline or hydroxy lysine
  6. 6. Triple helical structureHydroxy proline and Hydroxy lysine
  7. 7. Glycosylation. The hydroxyl group of hydroxylysine residues of collagen may be enzymatically glycosylated.Most commonly glucose and galactose are sequentially attached to the polypeptide chain prior to triple helix formation.
  8. 8. BIOSYNTHESIS OF COLLAGENThe polypeptide precursors of collagen molecule are formed in the fibroblasts(or in the related osteoblasts of bone and chondroblasts of cartilage),and are secreated into the extracellular matrix.After enzymatic modification,mature collagen monomers aggregate and become crosslinked to form collagen fibrils.
  9. 9. 1.Formation of pro-α-chains.2.Hydroxylation3.Glycosylation4.Assembly and secretion5.Extracellular cleavage of procollagen molecules.6.Formation of collagen fibrils.7.Cross linked formation
  10. 10. DEGRADATION OF COLLAGEN Normal collagens are highly soluble molecules,having half lives as long as several months.However the connective tissue is dynamic and is constantly being remodeled,often in response to the growth or injury of the tissue.Breakdown of collagen is done by:COLLAGENASESMATRIX PROTEINASES
  11. 11. Collagen diseasesMore than 100 mutations have been identified in 22 genes coding for twelve of the collagen types.1.Ehlers-Danlos syndrome(EDS)Hetrogeneous group of connective tissue disorders that result from inheritable defects in the metabolism of fibrillar collagen molecules.
  12. 12. EDS can result from collagen processing enzymes (lysyl- hydroxylase deficiency or procollagen peptidase deficiency).Mutations in the amino acid sequences of collagen types I.III,Or V.The most clinically important mutations are found in the gene for type III collagen.Collagen containing mutant chains is not secreated,and is either degraded or accumulated to high levels in intracellular compartments.Mutations in type 1 collagen fibrils results in stretchy skin and loose joints
  13. 13. 2.Osteogenesis imperfecta (OI)Also known as brittle bone syndrome.Retarted wound healing and a rotated and twisted spine leading to a “humped-back” appearances are common features of the disease.
  14. 14. Type 1 OI,Osteogenesis imperfect tarda.Presents in early infancy with fractures secondary to minor trauma,and may be suspected if prenatal ultrasound detects bowing or fractures of lonf bones.Type 2 OI,Osteogenesis imperfecta congenitaMore severe.Patients die in utero.Mutations in the αChains of type 1 collagen.Subsitution of glycine with aminoacids containing bulky side chains which hinder in the formation of triple helix of collagen.
  15. 15. ELASTINConnective tissue protein with rubber like properties.Elastic fibers composed of elastin and glycoprotein microfibrils are found in lungs.the walls of large arteries,and elastic ligaments.They can be stretched to several times their normal length but recoil to their original shape when the stretching force is relaxed.
  16. 16. Structure of elastinElastin is insoluble protein polymer.Synthesized from precursor,tropoelastin,which is a linear polypeptide composed of 700,that are primarily small and non polar.Elastin is also rich in proline and lysine,but contains only a little hydroxyproline and NO hydroxylysine.
  17. 17. Tropoelastin secreted by the cell into the extracellular space interacts with the specific gycoprotein microfibrils,such as fibrilin.Mutations in the fibrilin gene are responsible for MARFAN’S SYNDROME.
  18. 18. 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 neighbouring polypeptides form a DESMOSINE cross link
  19. 19. ROLE OF α₁-ANTITRYPSIN INELASTIN DEGRADATIONα₁ ANTITRYPSIN.Plasma proteinHas impportant physiological role of inhibiting neutrophil elastase.Role of α₁ antitrypsin in the lungs .
  20. 20. Emphysema resulting from α₁ ANTITRYPSIN deficiency.A number of different mutations in the α₁ antitrypsin gene are known to cause a deficiency of this protein,but one single purine base mutation(GAG- AAG),resulting in the substitution of lysine for glutamic acid at position 342 is clinically the most widespread.
  21. 21. A specific methionine in α₁-antitrypsin is required for the binding of the ihibitor to its target proteases.Smoking causes the oxidation and sebsequent inactivation of methinine residue,thereby rendering the inhibitor powerless to neutralize elastase.
  22. 22. Primary structure The sequence,type and number of aminoacids in a protein is called the primary structure of protein.Understanding the primary structure of protein is important because many genetic diseases result in protein with abnormal aminoacid sequences,which cause improper folding and loss or impairment of normal function.If the primary structure of normal and mutated protein is known,this information may be used to diagnose or study the disease.
  23. 23. Secondary structure of proteinSecondary structure, referrs to the local conformation of some part of the polypeptide.αHelix, β sheet, β Bends and motifs is example of secondary structure of proteins.Paul and Corey predicted the existence of these secondary structures in 1951.
  24. 24. α HELIXSeveral different types of helices but α helix is the most abundant.It is a spiral structure consisting of a tightly packed, coiled polypeptide backbone core,with the side chains of the component aminoacids extending outward from the central axis to avoid interfering sterically with eachother.
  25. 25. Characteristics of α HelixI t is right handed.It is stablized by the extensive hydrogen bonding between the peptide bond carbonyl oxygens and amide hydrogens that are part of polypeptide backbone.The hydrogen bonding is present between the successive first and fourth amino acid.
  26. 26. Each turn of the αHelix contains 3.6 aminoacid.Thus,aminoacid residues spaced three or four apart in the primary sequence are spatially close together when folded in the αhelix.
  27. 27. Five different kinds of constraints affect the stability of an a helix:1. The electrostatic repulsion (or attraction) between successive amino acid residues with charged R groups.2. The bulkiness of adjacent R groups.3. The interactions between amino acid side chains spaced three (or four) residues apart.4. The occurrence of Pro and Gly residues.5. The interaction between amino acid residues at the ends of the helical segment .
  28. 28. βSHEETβ SHEET is another form of secondary structure in which all the peptide bond components are involved in hydrogen bonding.The surface of β sheet appear “pleated” and therefore these structures are often called β pleated sheets .When illustrations are made of protein structures, β strands are often visualized as broad arrows.The adjacent polypeptide chains in a β sheet can be either parallel or antiparallel.
  29. 29. The β conformation of polypeptide chains. These top andside views reveal the R groups extending out from the β sheet and emphasize the pleated shape described by the planes of the peptide bonds
  30. 30. βBENDSβ Bends reverse the direction of polypeptide chain,helping it to form a compact globular shape.In globular proteins, which have a compact folded structure, nearly one-third of the amino acid residues are in turns or loops where the polypeptide chain reverses direction.They are usually found on the surface of protein molecule ,and often includes charged residues.
  31. 31. Particularly common are β turns that connect the ends of two adjacent segments of an antiparallel β sheet.The structure is a 180º turn involving four amino acid residues, with the carbonyl oxygen of the first amino acid residue forming a hydrogen bond with the amino- group hydrogen of the fourth.
  32. 32. The peptide groups of the central two residues in b turns do not participate in any interresidue hydrogen bonding.Gly and Pro residues often occur in b turns.
  33. 33. Structures of β turns
  34. 34. MOTIFSGlobular proteins are constructed by combining secondary structural elements(α Helices,β sheet).
  35. 35. TERTIARY STRUCTURE OFPROTEINS Tertiary Structure describes the shapes which form when the secondary spirals of the protein chain further fold up on themselves.The overall three-dimensional arrangement of all atoms in a protein.
  36. 36. DOMAINS are the fundamental functional and three dimensional structural units of a polypeptide.Polypeptide chains that are greater than 200 aminoacids in length consists of two or more domains.The core of the domain is built from super secondary elements(motifs)
  37. 37. Folding of the peptide chain within a domain usually occurs independentlay of folding in others domain.Therefore each domain has a characteristics of a small compact globular protein that is structurally independent of the other domains in the polypeptide chain.
  38. 38. Interactions stablizing tertiary structureThe unique three dimensional structure of each polypeptide is determined by the aminoacid sequence.Interactions between the side chains of aminoacids guide the folding of the polypeptide to form the compact structure .Four types of interactions cooperate in stablizing the tertiary structure of globular proteins.
  39. 39. Disulfide bondHydrophobic interactionsHydrogen bondsIonic interactions
  40. 40. QUATERNARY STRUCTURE Some proteins contain two or more separate polypeptide chains or subunits.The arrangement of these protein subunits in three-dimensional complexes constitutes quaternary structure.For example globin of hemoglobin is made up of four subunit,Enzyme pyruvate dehydrogenase is madeup of three subunits
  41. 41. Protein undergo assisted foldingA specialized group of proteins, named chaperones are required for the proper folding of many species of proteins.Molecular chaperones: Hsp 70, Hsp 40, Dna K, Dna J, Grp E, chaperonins…etc.Protein disulfide isomerase (PDI): catalyzes the interchange or shuffling of disulfide bonds.Peptide prolyl cis-trans isomerase (PPI): catalyzes the interconversion of the cis and trans isomers of proline peptide bonds.
  42. 42. Protein misfoldingProtein folding is a complex,trial and error process that can some times result in improperly folded molecules.Deposits of misfolded proteins are associated with a number of diseases including1.Amyloidoses2.Prion disease