Structural Proteins (PDF)

Kwame Nkrumah University of Science & Technology, Kumasi, Ghana STRUCTURAL PROTEINS IVY OFORI BOADU,MLS, (PhD), FWAPCMLS Department of Medical diagnostics FAHS, KNUST I. BOADU  Lecture Outline...

Kwame Nkrumah University of Science & Technology, Kumasi, Ghana STRUCTURAL PROTEINS IVY OFORI BOADU,MLS, (PhD), FWAPCMLS Department of Medical diagnostics FAHS, KNUST I. BOADU  Lecture Outline Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Proteins structure Collagen Elastin Keratin I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana LEARNING OBJECTIVES To discuss function and structure of protein To explain the various structural proteins Collagen synthesis and its disorders Elastin and its disorders Keratin I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana I. BOADU  Proteins Kwame Nkrumah University of Science & Technology, Kumasi, Ghana POLYMERS OF L -α AMINO ACIDS Most structurally & functionally diverse group of biomolecules Classification Functions Chemical nature and solubility Nutritional status I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Functions of proteins involved in almost everything Catalytic (enzymes ) (pepsin, polymerase, etc.) structure (keratin, collagen) carriers & transport (albumin, transferin) receptors & binding (immunoglobulins, antibodies) contraction (actin & myosin) storage (ovalbumin, FERRITIN) Regulatory (insulin, growth hormones I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Chemical nature and solubility Simple- made up of only amino acids, ( albumin, globulin, collagen, elastin) Conjugated made up of proteins plus prosthetic group (glycoproteins, lipoproteins) Derived – combination of simple and conjugated proteins (coagulated proteins, proteans, metaproteins) I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Nutritional classification Complete- contains all essential amino acids (egg albumen, casein) Incomplete- lacks one essential amino acid (cereals deficient in lysine) Poor - lack more than one essential amino acids. (zein lacks tryptophan, lysine) I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Proteins Structure: monomer = amino acids 20 different amino acids polymer = polypeptide protein can be one or more polypeptide chains folded & bonded together large & complex molecules complex 3-D shape I. BOADU  Kwame Nkrumah University of Amino acids Science & Technology, Kumasi, Ghana ▪ Structure: ◆ central carbon ◆ amino group ◆ carboxyl group (acid) ◆ R group (side chain) ▪ variable group ▪ confers unique O H chemical properties of the amino acid H | || —C—C—OH —N— H | I. BOADU R  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Structure of proteins Primary Secondary Tertiary Quaternary I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Primary (1°) structure AA arranged in a linear structure joined by polypeptide bonds Order of amino acids in chain amino acid sequence determined by gene (DNA) slight change in amino acid sequence can affect protein’s structure & it’s function even just one amino acid change can make all the difference! I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Secondary (2°) structure Primary structure folded along its chain “Local folding” folding along short sections of polypeptide interaction between adjacent amino acids H bonds between R groups -helix -pleated sheet I. BOADU  Kwame Nkrumah University of Tertiary (3°) structure Science & Technology, Kumasi, Ghana When secondary structure is folded in 3D “Whole molecule folding” determined by interactions between R groups hydrophobic interactions effect of water in cell anchored by disulfide bridges (H & ionic bonds) I. BOADU  Kwame Nkrumah University of Quaternary (4°) structure Science & Technology, Kumasi, Ghana More two or more polypeptide chain joined together only then is it a functional protein hydrophobic interactions I. BOADU hemoglobin  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Protein structure (review) R groups hydrophobic interactions, disulfide bridges 3° multiple polypeptides hydrophobic 1° interactions aa sequence peptide bonds determined 2° by DNA R groups 4° H bonds I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana STRUCTURAL PROTEINS Structural proteins are a category of proteins providing support to major structures such as bones, skin, cartilage, hair, and muscles. This group includes proteins such as collagen elastin keratin. I. BOADU Collagen Kwame Nkrumah University of Science & Technology, Kumasi, Ghana The name ‘collagen’ comes from Greek meaning ‘glue producer’. When heated in water , it gradually breaks down to produce soluble derived protein i.e. gelatin or animal glue. A family of fibrous proteins found in all multi- cellular animals. They are secreted by connective tissue cells, as well as by a variety of other cell types. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Collagen The most abundant protein in mammals i.e. ¼ of total body weight. 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 The major fibrous element of skin, bone, tendons, cartilage, blood vessels and teeth. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Collagen It comprises about 90% of the organic matrix of the bone Has a structural role in mature tissue and a directive role in developing tissue In some tissues, collagen may be dispersed as a gel that gives support to the structure, as in the extracellular matrix or the vitreous humor of the eye. Forms the insoluble fibers of high tensile strength. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Collagen structure Most abundant protein Triple helix Made up of polypeptide chains Each polypeptide contains 1000 amino acids GLYCINE-X-Y most abundant AA in collagen. about 30% the weight Proline Hydroxyproline lysine I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Principal Amino Acids found in Collagen I. BOADU  Kwame Nkrumah University of Types of Collagen Science & Technology, Kumasi, Ghana different types , 4 common types Variation is as a result of the amino acid sequence of the α chain which give rise to structural components that are about the same size (approximately 1,000 amino acids long) but with slightly different properties. Type Distribution I Skin, tendon, bone cartilage II Cartilage, vitreous humour III Fetal skin, cardiovascular system, lung vessels IV Basement Membrane I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Types of collagen Fibril-forming collagens- the fibrillar collagens and have the rope-like structure described for a typical collagen molecule. These fibril gives the collagen its characteristic tensile strength. Network-forming collagens -form a three-dimensional mesh, rather than distinct fibrils. Fibril-associated collagens. bind to the surface of collagen fibrils, linking these fibrils to one another and to other components in the extracellular matrix I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Synthesis of collagen Amino acid sequencing Collagen is rich in proline and glycine.(hydroxyproline and hydroxy lysine) Proline facilitates the formation of the helical conformation of each α chain Glycine, the smallest amino acid, is found in every third position of the polypeptide chain. It fits into the restricted spaces where the three chains of the helix come together I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Synthesis of collagen- hydroxylation Collagen contains hydroxyproline and hydroxylysine These residues result from the hydroxylation of some of the proline and lysine residues after their incorporation into polypeptide chains. Proline is the precursor of hydroxyproline lysine is the precursor of hydroxylysine Enzyme-Prolyl hydroxylase—has ferrous ion at its active site Converts certain proline residues into hydroxyproline Requires ascobate (reducing agent) to keep ferrous iron of prolyl hydroxylase reduced I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Glycosylation The hydroxyl group of the 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. I. BOADU  Synthesis of collagen Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Individual collagen polypeptide chains are synthesized on membrane-bound ribosomes and injected into the lumen of the endoplasmic reticulum (ER) as larger precursors, called pro- chains In the lumen of the ER, selected prolines and lysines are hydroxylated to form hydroxyproline and hydroxylysine, respectively, and some of the hydroxylysines are glycosylated. Each pro- chain then combines with two others to form a hydrogen-bonded, triple-stranded, helical molecule known as procollagen I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Collagen synthesis Preprocollagen------signal peptidase Procollagen----------procollagen peptidases formation of disulphide bonds and triple helix. Tropocollagen----- amino and carboxyl propeptidase and cross linkages to form collagen. I. BOADU Synthesis of Collagen Kwame Nkrumah University of Science & Technology, Kumasi, Ghana I. BOADU  Kwame Nkrumah University of Collagenases Science & Technology, Kumasi, Ghana Enzyme that cleaves peptide bonds located in the characteristic helical regions of collagen. Collagenase secreted clostridium histolyticum cause gas gangrene. This Splits collagen at more than 200 sites I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Collagen disorders Defects in any one of the many steps in collagen fiber synthesis can result in a genetic disease involving an inability of collagen to form fibers properly. This results in the inability to provide tissues with the needed tensile strength normally provided by collagen. I. BOADU Scurvy Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Caused by a dietary deficiency of ascorbic acid. The iron in the proline hydroxylase is not kept reduced. Synthesized collagen is not properly hydroxylated and has a lower melting temperature. The abnormal collagen cannot properly form fibres and leads to skin and other connective tissue lesions. I. BOADU Scurvy Kwame Nkrumah University of Science & Technology, Kumasi, Ghana I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Scurvy: features in infants Painful tender limbs. Defective bone formation. Weak blood vessels with haemorrhages. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Scurvy: features in adults Bleeding from the gums and around hair follicles. Bleeding into joints. Poor wound healing. Loose teeth. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Clinical Features of Scurvy Anaemia Abnormal wound healing Fatigue or weakness I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Ehlers-Danlos syndrome A group of hereditary disorders in which collagen synthesis is impaired. Defect in type III collagen synthesis. Deficiency of procollagen peptidases. Defective hydroxylation of lysine. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Ehlers-Danlos syndrome- Features Hyper extensibility of joints Excessive stretching of skin. Ready bruising and easy tearing of skin I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana I. BOADU Ehlers-Danlos syndrome- Features Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Hyper-mobile joints I. BOADU Osteogenesis Imperfecta Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Osteogenesis imperfecta is a group of genetic bone disorders. Caused by defective type I collagen. Caused by mutation of a single glycine (change in residue 988 from glycine to cysteine) Disruption of the triple helix near its carboxyl end exposing it to excessive hydroxylation and glycosylation. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Osteogenesis Imperfecta Abnormal collagen partly unfolds at body temperature and cannot form highly ordered fibrillar arrays. A change in a single nucleotide in a genome produces a fatal disorder. There are four recognized types of OI: type I, II, III, IV. I. BOADU  Kwame Nkrumah University of Clinical Features of type I OI Science & Technology, Kumasi, Ghana Most common and mildest type of OI. Bones fracture easily. Most fractures occur before puberty. Normal or near-normal stature. Loose joints and muscle weakness. Sclera (whites of the eyes) usually have a blue, purple, or gray tint. I. BOADU  Kwame Nkrumah University of Clinical Features of type I OI Science & Technology, Kumasi, Ghana Tendency toward spinal curvature. Brittle teeth possible. Hearing loss possible, often beginning in early 20s or 30s. Collagen structure is normal, but the amount is less than normal. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Elastin I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Elastin The main component of elastic fibers is elastin. Confers elasticity or recoil to lung tissues vessels and tendons. A highly hydrophobic protein, which, like collagen, is unusually rich in proline and glycine. But, unlike collagen, is not glycosylated. Contains some hydroxyproline but no hydroxylysine I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Formation of elastic network Soluble tropoelastin (the biosynthetic precursor of elastin) is secreted into the extracellular space and assembled into elastic fibers close to the plasma membrane. After secretion, the tropoelastin molecules become highly cross-linked to one another, generating an extensive network of elastin fibers and sheets. The cross-links are formed between lysines by a mechanism similar to that of collagen molecules I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Elastin structure The elastin protein is composed largely of two types of short segments that alternate along the polypeptide chain: hydrophobic segments, which are responsible for the elastic properties of the molecule; and alanine- and lysine-rich a-helical segments, which form cross-links between adjacent molecules I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Elastin disorders Williams syndrome Spontaneous deletion of genes. This gene is part of the proteins that produces elastin. Gene deletion occurs during the formation phase of the embryo and may vary per individual. Symptoms Short stature Wide mouth Puffyness around the eye I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Keratin I. BOADU  Kwame Nkrumah University of Keratins Science & Technology, Kumasi, Ghana refers to a family of fibrous structural proteins. its the key of structural material making up the outer layer of human skin It is also the key structural component of hair and nails. Keratin monomers assemble into bundles to form intermediate filaments, I. BOADU  Keratins Kwame Nkrumah University of Science & Technology, Kumasi, Ghana They are tough and insoluble and form strong unmineralized tissues found in reptiles, birds amphibians, and mammals. Two important classes of proteins that have similar amino acid sequences and biological function are called -and -keratins. -keratin - helix structure Hair, horns, nails, claws and hooves of mammals. -keratins-  sheet structure Scales and claws of reptiles, their shells, the feathers, beaks, claws of birds and quills of porcupines I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Disulfide bridges Keratins have large amounts of the sulfur-containing amino acid cysteine. The cysteine is required for the disulfide bridges that confer additional strength and rigidity. Human hair is approximately 14% cysteine. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Disulfide bridges The pungent smells of burning hair and rubber are due to the sulfur compounds formed. Extensive disulfide bonding contributes to the insolubility of keratins. The fewer the inter-chain disulfide bridges in keratins, the more flexible it is. I. BOADU -keratins Kwame Nkrumah University of Science & Technology, Kumasi, Ghana The major proteins of hair and fingernails and compose a major fraction of animal skin. Members of a broad group of intermediate filament proteins. -keratin has an unusually high content of cysteine I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana -keratins structure (hair) The individual -keratin molecules contain long sequences-that are wholly -helical. Pairs of these helices intertwine. In hair, two of the coiled coils then further twist together to form a 4-molecule protofibril. I. BOADU -keratins structure (hair) Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Eight protofibrils combine to make the microfibril that is the basis of hair structure. Hundreds of these microfibrils are cemented into an irregular bundle called a macrofibril. These in turn are mixed with dead and living cells to make a complete strand of hair. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Hardened hair Such twisted cables are stretchy and flexible, but in different tissues - keratin is hardened, to differing degrees, by the introduction of disulfide cross-links within the several levels of fiber structure I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Looking beautiful? The process of introducing a "permanent wave" into human hair involves: 1. reduction of these disulfide bonds, 2. rearrangement of the fibers, and 3. reoxidation to "set" the waves thus introduced I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana SUMMARY structural proteins are widespread mutation in a gene that codes for any of these proteins can have severe detrimental effects. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana How is it done? A basic reducing substance (usually ammonium thioglycolate) is added to reduce and rupture some of the disulfide cross-links Temporary Wave Permanent wave When the hair gets wet, water The hair is put on rollers or curlers. molecules intrude into the keratin The alpha-helices can shift positions. strands disrupting some of the An oxidizing agent, usually a dilute hydrogen bonds which also help to solution of hydrogen peroxide, is keep the alpha-helices aligned. When added to reform the disulfide bonds hair is dried up, the hair strands are in their new positions. The permanent able for a short time to maintain the will hold these new disulfide bond new curl in the hair. positions until the hair grows out. I. BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana THANK YOU QUESTIONS?????? I. BOADU