Protein Functions: catalyze reactions (enzymes) receptors (eg. pain receptors) transport (ions...
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Protein Functions:
catalyze reactions (enzymes)
receptors (eg. pain receptors)
transport (ions across membranes, oxygen in blood)
molecular motors
recognition (eg. antibodies)
signals (eg. insulin)
structural support
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Protein structure
chains of amino acids4 levels of structurerange of functional groups
carb. acidsamidesamineshydroxylthiolaromatic rings
interact with other proteins: assembliesflexibility, movement (doors, hinges, levers, etc.)
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Amino acids:
20 building blocks
characterized by R group
in nature, S (L) configuration
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Notice: glycine is not chiral! Conformationally free
Hydrophobicside-chains
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Proline: side chain is bonded to main chain amine
conformationally restricted - effect on structure
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Aromatic
planar
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Hydroxyl
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Thiol
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Cysteine thiols can form disulfide linkages
important for 3, 4 structure
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Positively charged
Lys: pKa ~ 10.8Arg: pKa ~ 12.5His: pKa ~ 6.0
Depends on environment!
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Question: Why is Lys more acidic than Arg?
Lys: pKa ~ 10.8Arg: pKa ~ 12.5
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Lys: pKa ~ 10.8Arg: pKa ~ 12.5
+ is stabilized in Arg“happier” with +
Arg less like to give up proton
Arg less acidic
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Acids
Amides
pKa of acid ~ 4.1
amides not acidic or basic!
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AA chain formed via peptide bonds - polypeptide
Carbox acid + amine forms amidelose water
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50-2000 amino acids: protein<50 amino acids: peptide (eg. insulin, spider venom)
primary structure: a.a. sequence
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AA sequence is specific to each protein/peptide
Sequence coded by DNA (gene): 3 base ‘codon’ encodes one amino acid, plus start/stop codons.
eg: GAC = aspartate
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Peptide bonds are planar: 6 atoms in a planeC, C, O, N, H, C
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Source of planarity: N is sp2
barrier to rotation about C-N bondfree rotation between C-C, N-Cflexibility/rigidity
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Notice: R group on opposite sides
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Peptide bonds are trans:
If cis, R groups clash
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Free rotation, but only some angles possible due to steric clashes - limits possible folding patterns
phi psi
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Secondary structure: helices
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R groups point outright handed/clockwise (alpha) found in proteins (energetically favorable)3.6 residues per turnH-bonds between main chain O and N 4 aa’s down (next slide)
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Ribbon form for depicting helices
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Secondary structure: Beta sheetfully extended: parallel, anti-parallelH-bond between main-chain N and O
R groups perpendicular
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Ribbon depiction of Beta-sheets
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hairpin turn
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Tertiary structure
(myoglobin) (oxygen carrier in muscle
heme prosthetic group (contains iron)
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Tertiary structure
Beta-sheet rich
many proteins have both helices and sheets
Notice loops (no regular structure, but often still ordered (not random).
Often act as doors or flaps
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A: space-fill picture of myoglobin;blue = chargedyellow - hydrophobic
B: cross-section:hydrophilic outsidehydrophobic inside
When unfolded, most proteins are insoluble in water
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Some proteins form distinct domains
CD4 cell-surface protein: HIV virus attaches to this
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Quaternary structure:22 hemoglobin
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F6P aldolase (use Jmol – 1L6W)
Notice:
Quaternary structure (homodecamer)‘tails’ tie subunits together
Beta barrel (conserved tert. structure motif)
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Primary structure determines higher structure, function
Classic study with ribonuclease
(cuts RNA)
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Enzyme loses function when denatured, reduced
regains activity when dialized
all the info necessary is contained in sequence (originally in DNA sequence!
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Primary structure (sequence) is easy to determine: sequence DNA
So shouldn’t we be able to predict structure from sequence?
Yes, in theory - but haven’t figured out yet!
Secondary structure prediction is somewhat accurate
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We can predict structure, function by sequence alignment
myoglobin: carries oxygen in musclehemoglobin: carries oxygen in bloodstructure and function are related: sequences are similar
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Protein structure is visualized by x-ray crystallography (Chapter 4)
Static picture - but proteins are dynamic!
Small peptides can be visualized by NMR - but complex!
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Proteins are often post-translationally modified
(in eukaryotes)
expands repertoire of 20 aa’s
eg. phosphorylation often turns proteins ‘on and off’