Transcript Prezentace aplikace PowerPoint

Jana Novotná
Functional Roles of Proteins
1. Dynamic function
transport
metabolic control
contraction
catalysis of chemical transformation
2. Structural function
bone, connective tissue
Classification of Proteins by
Bioloical Function
1.
Enzymes (lactate dehydrogenase, DNA polymerase)
2.
Storage proteins (ferritin, cassein, ovalbumin)
3.
Transport proteins (hemoglobin, myoglobin, serum albumin)
4.
Contractile proteins (myosin, actin)
5.
Hormones (insulin, growth hormone)
6.
Protective proteins in blood (antibodies, complement, fibrinogen)
7.
Structural proteins (collagen, elastin, glycoproteins)
Protein Structure
Two broad classes of structure
1. globular proteins
2. fibrous proteins.
Globular proteins are compactly folded and coiled.
Fibrous proteins are more filamentous or elongated.
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Small peptides (containing less than a couple of dozen amino acids) are
called oligopeptides.
Longer peptides are called polypeptides.
Peptides have a "polarity"; each peptide has only one free a-amino group (on the
amino-terminal residue) and one free (non-sidechain) carboxyl group (on the
carboxy-terminal residue)
Primary Structure
Aids in understanding of:
protein structure
mechanism of action on molecular level
interrelationship with other proteins in
evolution
Sequencing of protein:
the study of protein modification
prediction of the similarity between two
proteins
The primary structure of peptides and proteins
refers to the linear number and order of the
amino acids present.
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the N-terminal end is to the left (the end
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bearing the residue with the free a-amino group)
the C-terminal end is to the right (the end
with the residue containing a free a-carboxyl group) .
Peptide bond formation
Knowledge of primary structure of
insulin aids in understanding its
synthesis and action.
1.
2.
3.
Pancreas produces single chain
precursor – proinsulin
Proteolytic hydrolysis of 35 amino
acid segment – C peptide
The remainder is active insulin
(two polypeptide chains A and B)
covalently joined by disulfide bonds
Amino acid identity in different animals:
Human, hors, rat, pig, sheep,chicken insulin
have differences only in residues 8, 9, and 10
of the A chain and residue 30 of the chain B
HIGHER LEVELS OF PROTEIN
ORGANIZATION
Secondary structure
Local conformation of polypeptide chain in the protein (atoms of the peptide bonds
and a-carbon are covalently interconected into the string, side chains R are not
included).
Tertiary structure
Three dimensional structure of polypeptide units (includes conformational
relationships in space of side chains R of polypeptide chain).
Quarternary structure
Polypeptide subunits noncovalently interact and organize into multisubunit protein
(not all proteins have quarternary structure).
The folding of the primary structure into native folding (secondary, tertiary and
quarternary structure) appears to occur in most cases spontaneously.
Cystein (disulfide) bonds are made after folding
Protein Secondary Structure
The alpha helix
a-helix is a right-handed coiled
conformation
• every backbone N-H group donates a
hydrogen bond to the backbone C=O group
of the amino acid four residues earlier
• 3.6 amino acid residues are per 360o turn
The formation of the a-helix is spontaneous
b–Structure
• Segments of polypeptide chains are
in extended helix with n = 2.
• 2 strands (segments) of polypeptide
chains are stabilized by H-bonding
between amide nitrogens and carbonyl
carbons.
• Polypeptide segments are aligned in
parallel or antiparallel direction to its
neighboring chains.
b-structure gives plated sheet appearance – side chain
groups are projected above and below the plane
generated by the hydrogen-bonded polypeptide chains.
b-structures are either parallel or antiparallel.
In parallel sheets adjacent peptide chains proceed in the same direction (i.e. the
direction of N-terminal to C-terminal ends is the same).
In antiparallel sheets adjacent chains are aligned in opposite directions.
Protein Tertiary Structure
Total three-dimensional structure of the polypeptide units of given
protein
The tertiary structure of a protein
Forces that give rise to tertiary structure
Hydrophobic
interaction
b plated sheets
a helical regions
Examples of the Tertiary Structure
Examples of a,b-folded domains in which bstructural strands form a b barrel in the center of the
domain
Examples of b-folded domains
Protein Quarternary Structure
Hemoglobin
Four subunits (two a and two b subunits) are associated in the quarternary structure
Forces Controlling Protein Structure
Hydrophobic interaction forces:
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Interaction inside polypeptide chains (amino acids contain either hydrophilic or
hydrophobic R-groups).
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Interaction between the different R-groups of amino acids in polypeptide chains
with the aqueous environment.
A nonpolar residues dissolved in water induces in the water solvent a solvation shell in which
water molecules are highly ordered.
Two nonpolar groups in the solvation shell reduce surface area exposed to solvent and come very
close come together.
Hydrogen Bonds:
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Proton donors and acceptors within and between polypeptide chains (backbone
and the R-groups of the amino acids).
H-bonding between polypeptide chains and surrounding aqueous medium.
Electrostatic Forces:
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Charge-charge interactions between oppositely charged R-groups such as Lys or
Arg (positively charged) and Asp or Glu (negatively charged).
Ionized R-groups of amino acids with the dipole of the water molecule.
van der Waals forces:
(Weak noncolvalent forces of great importance in protein structure)
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Attractive van der Waals forces - the interactions among induced dipoles that occur
between adjacent uncharged non-bonded atoms.
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Repulsive van der Waals forces - the interactions, when uncharged non-bonded
atoms come very close together but do not induce dipoles. The repulsion is the result
of the electron-electron repulsion that occurs as two clouds of electrons begin to
overlap.
Types of proteins
Globular proteins
Spheroid shape
Variable molecular weight
Relatively high water solubility
Variety function roles – catalysts, transporters, control proteins (for the
regulation of metabolic pathways and gene expression)
Fibrous proteins
Rodlike shape
Low solubility in the water
Structural role in the organism
Lipoproteins
Complex of lipids with protein
Glycoproteins
Contain covalently bound carbohydrate
Fibrous proteins
Collagen, elastin, a-keratin, and tropomyosin
Collagen
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high concentration in all organs
half total body proteins (by
weight)
tensil strenght and
elasticity
- tendons
- cartilages
- bone
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insoluble glycoprotein
- protein + carbohydrate
protein
- high glycine and modified aminoacids
(Gly-X-Y)
- hydroxyproline
- hydroxylysine
carbohydrate
- glucose
- galactose
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Lipoproteins
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Multicomponent complex of protein and lipids.
Molecular aggregate with approximate stoichiometry
between two components.
Wide variety function in blood (transport of lipids from
tissue to tissue), lipid metabolism.
Apolipoprotein = purified protein component of lipoprotein
particle
Four classes of blood plasma lipoproteins
(according their density):
1.
2.
3.
4.
High density lipoprotein (HDL) – apolipoprotein A-I,
(ApoA-I)
Low density lipoprotein (LDL) – ApoB-100
Intermediate density lipoprotein (IDL) - ApoB-100
Very low density lipoprotein (VLDL) - ApoC
Glycoproteins
Covalently attached sugar molecules at one or multiple
points along the polypeptide chain
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proteins secreted from cells
- hormones
- extracellular matrix proteins
- proteins involved in blood coagulation
- antibodies
- muscus secretion from epithelial cells
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Protein localized on surface of cells
- receptors (transmit signals of hormones or growth factors from
outside environment into the cell)
Structure-Function Relationship of
Protein Families
Antibodies
Immunoglobulin molecules have a
tetrammeric structure
Two H - heavy chains
Two L – light chains
Immunoglobulin classes:
IgG
IgM
IgA
IgD
IgE
heavy chain
g
m
a
d
e
Contractile elements of muscles
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Myosin – thick filament of the
muscle
Actin – thin filament of the muscle
G-actin (globular actin)
F-actin (fibrilar actin)
Tropomyosin
Troponin
Scheme of the myosin molecule
One of the biologically important
properties of myosin is its ability to
combine with actin and the muscle
produces force.
Model of myosin filament
Biological membrane proteins
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Integral membrane proteins
Peripheral membrane proteins
Channels and pores
Erythrocyte membrane
Diagram of a voltage-sensitive sodium channel α-subunit. G - glycosylation, P- phosphorylation, S - ion selectivity, I inactivation, positive (+) charges in S4 are important for transmembrane voltage sensing.
Membrane receptors
1.
2.
3.
b polypeptide stretch
extendings from a helix.
Seven membrane-spanning
domains.
Recognize catecholamines,
principally norepinephrine.
Hormone activates receptor.
Hormone-receptor mediated
stimulation of intracellular
signalling cascade.
Proposed model for insertion of the b2 adrenergic receptor in
the cell membrane
Proteolytic enzymes
Proteolytic enzymes are classified based on their
catalytic mechanism
Substrate binding site catalytically hydrolyze peptide bonds
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Serine-proteases (utilize an activated serine residuein
substrate binding site)
Cysteine-proteases (utilize an activated cysteine
residue)
Aspartate-proteases (utilize an activated aspartate
residue)
Metallo-proteases (utilize an activated metal ion)
DNA binding proteins
Regulatory proteins binding to DNA sequence can promote either
an activation or repression of the rate of gene transcription into
mRNA
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Helix-turn-helix binding proteins
The zinc finger motif
The leucine zipper motif
The zinc finger motif
Helix-turn-helix motif
Hemoglobin and myoglobin
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Human hemoglobin occurs in
several forms.
Consist of four polypeptide chains
of two different primary structure.
Bind oxygen in the lung and
transport the oxygen in blood to
the tissues and cells.
•Myoglobin is a single polypeptide
chain with one oxygen binding site.
•Binds and release oxygen in cytoplasm
of muscle cells.
•Hemoglobin and myoglobin molecules
each contain a heme prosthetic group.
•Protein without prosthetic group is
designated as apoprotein.
•Complete protein is a holoprotein
Internet links
http://student.ccbcmd.edu/~gkaiser/biotutorials/proteins/images/alphahelix.jpg
http://chem.ps.uci.edu/~pfarmer/grp2/myoglobin.jpg
http://cs.wikipedia.org/wiki/Hemoglobin
http://academic.brooklyn.cuny.edu/biology/bio4fv/page/tertie.gif
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Polypeptides.html
http://www.mun.ca/biology/scarr/Collagen_structure.gif
http://academic.brooklyn.cuny.edu/biology/bio4fv/page/prot_struct-4143.JPG
http://academic.wsc.edu/faculty/jatodd1/351/actin_myosin.jpg