PROTEIN FUNCTIONS
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SIGNIFICANCE OF PROTEIN FUNCTIONS IN MEDICINE
Example:
• protein: dystrophin
• disease: Duchenne muscular dystrophy
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PROTEIN FUNCTIONS:
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The relationship of structure and function of proteins
Protein families
Functional polymers and complexes of proteins
Binding of other molecules to proteins
Regulation of protein activity
Regulated protein degradation
Functional types of proteins
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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.]
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The shape of protein molecule:
• Globular proteins
• Fibrous proteins
• Protein domain
[FIG.]
• Disulfide bonds
[FIG.]
• Chaperones
Protein function results from its structure.
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The shape of protein molecule:
• Globular proteins
• Fibrous proteins
• Protein domain
[FIG.]
• Disulfide bonds
[FIG.]
• Chaperones
Protein function results from its structure.
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The shape of protein molecule:
• Globular proteins
• Fibrous proteins
• Protein domain
[FIG.]
• Disulfide bonds
[FIG.]
• Chaperones
Protein function results from its structure.
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2. PROTEIN FAMILIES:
They include proteins similar in their structure and function.
[FIG.]
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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.]
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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.]
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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.]
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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.]
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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.]
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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)
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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)
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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
• Phosphorylation: protein kinase, phosphatase
• 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)
• Positive regulation
[FIG.]
[FIG.]
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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
• Phosphorylation: protein kinase, phosphatase
• 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)
• Positive regulation
[FIG.]
[FIG.]
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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
• Phosphorylation: protein kinase, phosphatase
• 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)
• Positive regulation
[FIG.]
[FIG.]
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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
• Phosphorylation: protein kinase, phosphatase
• 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)
• Positive regulation
[FIG.]
[FIG.]
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6. REGULATED PROTEIN DEGRADATION:
Enzymatic degradation: proteolysis, proteases
Proteasome
Ubiquitin
[FIG.]
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7. FUNCTIONAL TYPES OF PROTEINS:
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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)
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LITERATURE:
• Alberts B. et al.: Essential Cell Biology. Garland Science. New York
and London, pp. 119­157 & 258­259, 2010.
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