PROTEIN FUNCTIONS 1

SIGNIFICANCE OF PROTEIN FUNCTIONS IN MEDICINE Example: protein: dystrophin disease: Duchenne muscular dystrophy 2

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PROTEIN FUNCTIONS: 1.The relationship of structure and function of proteins 2.Protein families 3.Functional polymers and complexes of proteins 4.Binding of other molecules to proteins 5.Regulation of protein activity 6.Regulated protein degradation 7.Functional types of proteins 5

1.THE RELATIONSHIP OF STRUCTURE AND FUNCTION OF PROTEINS: Protein structure is defined on several levels : 1.Primary structure 2.Secondary structure 3.Tertiary structure 4.Quaternary structure (oligomer)[FIG.] 6

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The shape of protein molecule: Globular proteins Fibrous proteins Protein domain[FIG.] Disulfide bonds[FIG.] Chaperones [FIG.] Protein function results from its structure. 8

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The shape of protein molecule: Globular proteins Fibrous proteins Protein domain[FIG.] Disulfide bonds[FIG.] Chaperones [FIG.] Protein function results from its structure. 10

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The shape of protein molecule: Globular proteins Fibrous proteins Protein domain[FIG.] Disulfide bonds[FIG.] Chaperones[FIG.] Protein function results from its structure. 12

13 Figure 6–86The Hsp70 family of molecular chaperones. T

The shape of protein molecule: Globular proteins Fibrous proteins Protein domain[FIG.] Disulfide bonds[FIG.] Chaperones[FIG.] Protein function results from its structure. 14

2.PROTEIN FAMILIES: They include proteins similar in their structure and function. Proteins of one protein family are coded by genes of one gene family. [FIG.] 15

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3.FUNCTIONAL POLYMERS AND COMPLEXES OF PROTEINS: Capability of protein molecules for self-organizing. [FIG.] Association into big polymers and the formation of various structures: Filaments (actin, elastin) [FIG.] [FIG.] Tubules (microtubules) [FIG.] Sheets (membrane proteins) Spheres (viral capsids) [FIG.] Protein complexes (molecules of various proteins, including other types of molecules) [FIG.] 17

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3.FUNCTIONAL POLYMERS AND COMPLEXES OF PROTEINS: Capability of protein molecules for self-organizing. [FIG.] Association into big polymers and the formation of various structures: Filaments (actin, elastin) [FIG.] [FIG.] Tubules (microtubules) [FIG.] Sheets (membrane proteins) Spheres (viral capsids) [FIG.] Protein complexes (molecules of various proteins, including other types of molecules) [FIG.] 19

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3.FUNCTIONAL POLYMERS AND COMPLEXES OF PROTEINS: Capability of protein molecules for self-organizing. [FIG.] Association into big polymers and the formation of various structures: Filaments (actin, elastin) [FIG.] [FIG.] Tubules (microtubules) [FIG.] Sheets (membrane proteins) Spheres (viral capsids) [FIG.] Protein complexes (molecules of various proteins, including other types of molecules) [FIG.] 22

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3.FUNCTIONAL POLYMERS AND COMPLEXES OF PROTEINS: Capability of protein molecules for self-organizing. [FIG.] Association into big polymers and the formation of various structures: Filaments (actin, elastin) [FIG.] [FIG.] Tubules (microtubules) [FIG.] Sheets (membrane proteins) Spheres (viral capsids) [FIG.] Protein complexes (molecules of various proteins, including other types of molecules) [FIG.] 24

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3.FUNCTIONAL POLYMERS AND COMPLEXES OF PROTEINS: Capability of protein molecules for self-organizing. [FIG.] Association into big polymers and the formation of various structures: Filaments (actin, elastin) [FIG.] [FIG.] Tubules (microtubules) [FIG.] Sheets (membrane proteins) Spheres (viral capsids) [FIG.] Protein complexes (molecules of various proteins, including other types of molecules) [FIG.] 26

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4.BINDING OF OTHER MOLECULES TO PROTEINS: Ligands: ligand binding is highly selective and directly related to the function of protein.[FIG.] Binding of ion/atom: Ca 2+ (calmodulin), Fe 3+ (transferrin) Binding of small nonprotein molecule: heme (hemoglobin), retinal (rhodopsin), saccharide (glykoproteins), phosphate (phosphorylated proteins), GTP (GTP binding proteins) Binding of nonprotein macromolecule: DNA (transcription factors) Binding of protein molecule: protein substrate (enzyme), protein antigen (antibody) 28

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4.BINDING OF OTHER MOLECULES TO PROTEINS: Ligands: ligand binding is highly selective and directly related to the function of protein.[FIG.] Binding of ion/atom: Ca 2+ (calmodulin), Fe 3+ (transferrin) Binding of small nonprotein molecule: heme (hemoglobin), retinal (rhodopsin), saccharide (glykoproteins), phosphate (phosphorylated proteins), GTP (GTP binding proteins) Binding of nonprotein macromolecule: DNA (transcription factors) Binding of protein molecule: protein substrate (enzyme), protein antigen (antibody) 30

5.REGULATION OF PROTEIN ACTIVITY: Allosteric molecules Conformational change → change in activity Mechanisms of protein activity regulation: Binding of ion/atom: IRP (iron regulatory protein) (Fe) Binding of small molecule : Glycosylation: glycoprotein[FIG.] Phosphorylation: protein kinase, phosphatase[FIG.] Binding of GTP: GTP-binding proteins Binding of protein: cyclin dependent kinase (cyclin) Proteolytic cleavage: insulin, caspases[FIG.] Regulation of enzyme activity: Negative regulation (feedback inhibition)[FIG.] Positive regulation 31

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5.REGULATION OF PROTEIN ACTIVITY: Allosteric molecules Conformational change → change in activity Mechanisms of protein activity regulation: Binding of ion/atom: IRP (iron regulatory protein) (Fe) Binding of small molecule : Glycosylation: glycoprotein[FIG.] Phosphorylation: protein kinase, phosphatase[FIG.] Binding of GTP: GTP-binding proteins Binding of protein: cyclin dependent kinase (cyclin) Proteolytic cleavage: insulin, caspases[FIG.] Regulation of enzyme activity: Negative regulation (feedback inhibition)[FIG.] Positive regulation 33

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5.REGULATION OF PROTEIN ACTIVITY: Allosteric molecules Conformational change → change in activity Mechanisms of protein activity regulation: Binding of ion/atom: IRP (iron regulatory protein) (Fe) Binding of small molecule : Glycosylation: glycoprotein[FIG.] Phosphorylation: protein kinase, phosphatase[FIG.] Binding of GTP: GTP-binding proteins Binding of protein: cyclin dependent kinase (cyclin) Proteolytic cleavage: insulin, caspases[FIG.] Regulation of enzyme activity: Negative regulation (feedback inhibition)[FIG.] Positive regulation 35

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5.REGULATION OF PROTEIN ACTIVITY: Allosteric molecules Conformational change → change in activity Mechanisms of protein activity regulation: Binding of ion/atom: IRP (iron regulatory protein) (Fe) Binding of small molecule : Glycosylation: glycoprotein[FIG.] Phosphorylation: protein kinase, phosphatase[FIG.] Binding of GTP: GTP-binding proteins Binding of protein: cyclin dependent kinase (cyclin) Proteolytic cleavage: insulin, caspases[FIG.] Regulation of enzyme activity: Negative regulation (feedback inhibition)[FIG.] Positive regulation 37

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5.REGULATION OF PROTEIN ACTIVITY: Allosteric molecules Conformational change → change in activity Mechanisms of protein activity regulation: Binding of ion/atom: IRP (iron regulatory protein) (Fe) Binding of small molecule : Glycosylation: glycoprotein[FIG.] Phosphorylation: protein kinase, phosphatase[FIG.] Binding of GTP: GTP-binding proteins Binding of protein: cyclin dependent kinase (cyclin) Proteolytic cleavage: insulin, caspases[FIG.] Regulation of enzyme activity: Negative regulation (feedback inhibition)[FIG.] Positive regulation 39

6.REGULATED PROTEIN DEGRADATION: Enzymatic degradation: proteolysis, proteases Proteasome Ubiquitin[FIG.] [FIG.] 40

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7.FUNCTIONAL TYPES OF PROTEINS: Structural proteins: tubulin, keratin, actin, collagen Enzymes: protein kinase C, DNA polymerase δ, pepsin Motor proteins: (molecular motors): myosin, kinesin, dynein Transport proteins: hemoglobin, transferrin, albumin Storage proteins: ferritin, casein, ovalbumin Signaling proteins: insulin, EGF, erythropoietin Receptor proteins: rhodopsin, insulin receptor, EGF receptor Regulatory proteins: chaperones, transcription factors, cyclins Antibodies Other proteins with special functions: GFP (green fluorescent protein) [FIG.] 43

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LITERATURE: Alberts B. et al.: Essential Cell Biology. Garland Science. New York and London, pp. 119­157 & 258­259,