protein functions: catalyze reactions (enzymes) receptors (eg. pain receptors) transport (ions...
Post on 20-Dec-2015
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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
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.)
Amino acids:
20 building blocks
characterized by R group
in nature, S (L) configuration
Notice: glycine is not chiral! Conformationally free
Hydrophobicside-chains
Proline: side chain is bonded to main chain amine
conformationally restricted - effect on structure
Aromatic
planar
Hydroxyl
Thiol
Cysteine thiols can form disulfide linkages
important for 3, 4 structure
Positively charged
Lys: pKa ~ 10.8Arg: pKa ~ 12.5His: pKa ~ 6.0
Depends on environment!
Question: Why is Lys more acidic than Arg?
Lys: pKa ~ 10.8Arg: pKa ~ 12.5
Lys: pKa ~ 10.8Arg: pKa ~ 12.5
+ is stabilized in Arg“happier” with +
Arg less like to give up proton
Arg less acidic
Acids
Amides
pKa of acid ~ 4.1
amides not acidic or basic!
AA chain formed via peptide bonds - polypeptide
Carbox acid + amine forms amidelose water
50-2000 amino acids: protein<50 amino acids: peptide (eg. insulin, spider venom)
primary structure: a.a. sequence
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
Peptide bonds are planar: 6 atoms in a planeC, C, O, N, H, C
Source of planarity: N is sp2
barrier to rotation about C-N bondfree rotation between C-C, N-Cflexibility/rigidity
Notice: R group on opposite sides
Peptide bonds are trans:
If cis, R groups clash
Free rotation, but only some angles possible due to steric clashes - limits possible folding patterns
phi psi
Secondary structure: helices
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)
Ribbon form for depicting helices
Secondary structure: Beta sheetfully extended: parallel, anti-parallelH-bond between main-chain N and O
R groups perpendicular
Ribbon depiction of Beta-sheets
hairpin turn
Tertiary structure
(myoglobin) (oxygen carrier in muscle
heme prosthetic group (contains iron)
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
A: space-fill picture of myoglobin;blue = chargedyellow - hydrophobic
B: cross-section:hydrophilic outsidehydrophobic inside
When unfolded, most proteins are insoluble in water
Some proteins form distinct domains
CD4 cell-surface protein: HIV virus attaches to this
Quaternary structure:22 hemoglobin
F6P aldolase (use Jmol – 1L6W)
Notice:
Quaternary structure (homodecamer)‘tails’ tie subunits together
Beta barrel (conserved tert. structure motif)
Primary structure determines higher structure, function
Classic study with ribonuclease
(cuts RNA)
Enzyme loses function when denatured, reduced
regains activity when dialized
all the info necessary is contained in sequence (originally in DNA sequence!
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
We can predict structure, function by sequence alignment
myoglobin: carries oxygen in musclehemoglobin: carries oxygen in bloodstructure and function are related: sequences are similar
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!
Proteins are often post-translationally modified
(in eukaryotes)
expands repertoire of 20 aa’s
eg. phosphorylation often turns proteins ‘on and off’