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Lecture 4
The structure andcom osition of roteins
BIOSCI 101: Cellular and Molecular Biology
Structure and composition of proteins Functions of proteins (50% or more of the dry
weight of most cells):-- provide many of the structural elements ofthe cell (cytoskeleton)- catalyse most of the reactions in the cell(enzymes)- act as contractile elements (muscle fibres)- act as transporters (membranes)
BIOSCI 101: Cellular and Molecular Biology
- act as regulators of cell metabolism(hormones, repressors etc)- act as food reserves (albumin)
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Structure and composition ofproteins (contd)
The diversity of protein function arisesbecause polypeptides fold in complex ways toyield a great diversity of precise 3D structures.This is, in turn, due to the 20 different aminoacids.
BIOSCI 101: Cellular and Molecular Biology
Amino acid structures (1)Nonpolar side chains; hydrophob ic
Side chain
Glycine(Gly or G)
Alan in e(Ala or A)
Valine(Val or V)
Leucine(Leu or L)
Isoleucine(I le or I )
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Methionine(Met or M)
Phenylalanine(Phe or F)
Tryptophan(Trp or W)
Proline(Pro or P)
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Amino acid structures (2)Polar side chains; hydrophi lic
Serine(Ser or S)
Threonine(Thr or T)
Cysteine(Cys or C)
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Tyrosine(Tyr or Y)
Asparagi ne(Asn or N)
Glutamine(Gln or Q)
Amino acid structures (3)
Electrically ch arged side chains; hydrophilic
Acidic (n egativel y charged)
BIOSCI 101: Cellular and Molecular BiologyCampbell 5.16c
Aspart ic acid(Asp or D)
Glutamic acid(Glu or E)
Lysine(Lys or K)
Arg in in e(Arg or R)
Histidine(His or H)
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Making apolypeptide
chain
Peptide bond
New p eptidebond forming
Sidechains
BIOSCI 101: Cellular and Molecular BiologyCampbell 5.17
Back-bone
Ami no end(N-terminus)
Peptidebond
Carboxyl end(C-terminus)
Proteins havea precise 3D
shape
BIOSCI 101: Cellular and Molecular BiologyCampbell 5.18
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BIOSCI 101: Cellular and Molecular BiologyCampbell 5.19
Primary ( 1 o ) structure
- the linear arrangement of amino acids
Protein structure
- the polypeptide has an amino terminusand a carboxy terminus- specified by the sequence ofnucleotides in DNA which is convertedinto information in protein via the mRNA
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Aminoacids
Amino end
PrimarystructurePrimary structure of transthyretin
BIOSCI 101: Cellular and Molecular BiologyCampbell 5.20
Carboxyl end
Protein structure (contd)
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Protein structure (contd) Secondary (2 o ) structure
- secondary structure is the localised
- consider the backbone of a polypeptide:
+
BIOSCI 101: Cellular and Molecular Biology
- the negatively and positively charged ends ofthe polar covalent N-H and C=O bonds canattract each other forming H bonds.
+
Protein structure (contd)
- the two most common folding patterns formedby H bonding between atoms of the peptide bondare the -helix and the -pleated sheet
- the actual secondary structure adopted will be
BIOSCI 101: Cellular and Molecular Biology
n uence y e groups
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helix
Secondary structure
Hydrogen bond pleated sheet
strand, shown as a flatarrow pointing towardthe carboxyl end
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Hydrogen bond
Protein structure (contd) Secondary structure (contd)
(a) the -helix- a rigid cylinder in which each peptide bond isregularly H-bonded to other peptide bondsnearby in the chain- found in the portions of transmembraneproteins that cross the lipid bilayer- occurs in the protein -keratin, found in skin,
BIOSCI 101: Cellular and Molecular Biology
hair, nails and feathers
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N-terminus
EXTRACELLULARSIDE
structure of a
transmembraneproteinhelix
C-terminus
BIOSCI 101: Cellular and Molecular BiologyCampbell 7.9
CYTOPLASMICSIDE
Protein structure (contd)
Secondary structure (contd)
(b) -pleated sheets- an extended polypeptide chain folds back andforth upon itself- held by H-bonds that connect the peptide bondsin neighbouring chains- found in the core of most lobular roteins
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- occurs in fibroin, the protein found in silk
(c) random coil - no regular structure - typicalwhen there are bulky R groups
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Protein structure (contd) Tertiary ( 3 o ) structure
-polypeptide chain
- the various segments of helix, pleated sheetand random coil are held in position bya) side chain interactions - hydrogen bondsand ionic bonds between hydrophilic R groupsand interactions between h dro hobic R
BIOSCI 101: Cellular and Molecular Biology
groups.b) intramolecular disulphide bonds - formbetween the two -SH groups of neighbouringcysteine residues in a folded polypeptide chain
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Protein structure (contd)
Tertiary structure (contd)
- proteins tend to fold in such a way as toarrange their hydrophobic groups towards theinterior and the hydrophilic groups towardsthe exterior of the molecule
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Bonds involved in tertiary
structure
Hydrogenbond
Disulfidebridge
Ionic bond
Hydrophobicinteractions andvan der Waalsinteractions
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Polypeptidebackbone
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Protein structure (contd)
Quaternary ( 4 o ) structure
- the number and relative positions of subunits ina multimeric protein- subunits are held together by interactionsbetween R groups- the subunits may be the same or different
BIOSCI 101: Cellular and Molecular Biology
Examples: Collagen (supercoiled triple helix)Human haemoglobin (2 -chains and 2
-chains)Microtubules (tubes of - and -
tubulin dimers)
Quaternary structure
Transthyretinprotein
(four identicalpolypeptides)
BIOSCI 101: Cellular and Molecular BiologyCampbell 5.20
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Examples of quaternary structure
Collagen
HemeIron
subunit
subunit
Tubulin
25 nm
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Hemoglobin
subunit
Review of protein structureSecondarystructure
Tertiarystructure
Quaternarystructure
Hydrogen bond
helix
pleated sheet strand
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Hydrogenbond
Transthyretinpolypeptide
protein
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Chaperonins assist proteins to
fold in cells
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Protein structure (contd) Denaturation and hydrolysis
- denaturation is unfolding of the 3-D shape of themolecule due to disruption of 2 o , 3 o and 4 ostructure (breakage of H bonds, hydrophilic andhydrophobic interactions and S=S bonds)- hydrolysis involves destruction of 1 o structure
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.- proteins can occasionally be reversiblydenatured (ribonuclease).
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Denaturation and renaturation
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Protein structure (contd)- denaturation may be achieved by :-
a) heat - breaks any weak bondb) extremes of pH changes ionisation
patterns of R groupsc) reducing agents - reduce S=S bonds to SHd) organic solvents - disturb hydrophobic and
hydrophilic interactionse) detergents disrupt hydrophobic
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interactions
- some examples of denaturation: albumin (eggwhite), collagen (gelatin)
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Test question
The 20 different amino acids found in polypeptides
because of different:1. alpha ( ) carbon atoms.2. asymmetric carbon atoms.3. carboxyl groups attached to the alpha
( ) carbon.
BIOSCI 101: Cellular and Molecular Biology
.carbon.
5. amino groups attached to the alpha( ) carbon.