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Levels of protein structure

Chem 40
2nd Sem 2012-2013 Lecture 10
FCario

1o = aa sequence; peptide bonds that link

aas togeether
2o = recurring arrangements in space of

3o: Spatial relationships among all aas

adjacent aa residues; H-bonds of aas close together in sequence

in polypeptide; complete 3-D structure of polypeptide

Primary structure
Amino acid sequence Amino carboxy termini Order of aa from amino carboxy
4o: number of subunits (polypeptide

chains)
Hetero- or homo Homomers heteromers

end Order of aas that form sequential peptide bonds

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Regular 2o structures
helices
-helices 3-10 helices helices

Irregular 2 structures
Loops of various sizes link elements of regular 2o structures together
Hairpin turns Longer loops

-sheets

Melted ribbons

- On average: ~31% in -helices, 28% in sheets, rest in irregular loops of varied sizes

A-helix: right handed favored because aas are L rod-like tightly coiled R chains point outward N-H interacting with C=O 4 aas ahead in chain (Amino to carboxy ends convention) hardly any H-bonding between R-chains

- Turn ( - bend, tight turn)

allows peptide chain to reverse direction carbonyl C of one residue is H-bonded to the amide proton of a residue three residues away proline and glycine prevalent
-bends or -turns; Type 1 more frequent

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Secondary types of structures

Predicting 2o structures
Molecular info for folding borne by the aa sequence Theoretically, if aa sequence known, prediction of 2o (and 3o) structures possible

Predicting 2o structures
Empirical methods most successful, based on known structures of specific proteins 1st studied by Chou and Fasman Tables compiled to show P, P, Pt for aa residues of proteins whose sequence structures were already empirically established

Predicting 2o structures
P, P, Pt relative frequency of finding aa residue in helices, -pleats, or turns P values can have predictive values, according to Chou-Fasman rules (old but still very illustrative) Used empirical data from aa composition and sequence of proteins already well characterized at the time (mainly via xray diffraction data) predictive algorithms written Ends of 2o structures hard to predict accurately

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Chou-Fasman rules - 1
Any segment of 6 residues or more, w/ [P] 1.03, and [P] > [P] and not including Pro, is predicted to be helix

Chou-Fasman rules-2
Any segment of 5 residues or more, w/ [P] 1.05, and [P] > [P], is predicted to be -sheet

Chou-Fasman rules - 3
Examine sequence for tetrapeptides (4 aa) with [P] < 0.9, [Pt] > [P ]. They are likely to be turns.

(Actual predictive rules are really a bit more complex, but this method frequently works)

THEREISSLAPDASHPERIPHERALASYMM ETRYINTEGRATEDWITHAFEWQWESTI NGSEMISANEMINDSANDSEMISENILE GENTLEMENANTICIPATINGSEVERALG IGGLINGGIRLS

THERE IS SLAP DASH PERIPHERAL ASYMMETRY INTEGRATED WITH A FEW QWESTING SEMI SANE MINDS AND SEMI SENILE GENTLEMEN ANTICIPATING SEVERAL GIGGLING GIRLS

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sample
THEREISSLAPDASHPERIPHERALASYMM ETRYINTEGRATEDWITHAFEWQWESTI NGSEMISANEMINDSANDSEMISENILE GENTLEMENANTICIPATINGSEVERALG IGGLINGGIRLS
Any segment of 6 residues or more, w/ [Pa] 1.03, and [Pa] > [Pb] and not including Pro, is predicted to be a helix

sample
THEREISSLAPDASHPERIPHERALASYMM ETRYINTEGRATEDWITHAFEWQWESTI NGSEMISANEMINDSANDSEMISENILE GENTLEMENANTICIPATINGSEVERALGIG
GLINGGIRLS
Any segment of 5 residues or more, w/ [Pb] 1.05, and [Pb] > [Pa], is predicted to be a -sheet

sample
THEREISSLAPDASHPERIPHERALASYMM ETRYINTEGRATEDWITHAFEWQWESTI NGSEMISANEMINDSANDSEMISENILE GENTLEMENANTICIPATINGSEVERALG IGGLINGGIRLS
Examine sequence for tetrapeptides (4 aa) with [Pa] < 0.9, [Pt] > [Pb]. They are likely to be turns

Turns??? THEREISSLAPDASHPERIPHERALASY MMETRYINTEGRATEDWITHAFEW QWESTINGSEMISANEMINDSAND SEMISENILEGENTLEMENANTICIPA TINGSEVERALGIGGLINGGIRLS

Examine sequence for tetrapeptides (4 aa) with [Pa] < 0.9, [Pt] > [Pb]. They are likely to be turns

Chou-Fasman
http://fasta.bioch.virginia.edu/fasta_www2/fa sta_www.cgi?rm=misc1 One of most commonly used algorithms Empirical, using data from characterized proteins

Protein structures
http://expasy.org/tools

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expasy.org/tools

expasy.org/tools
Chou-Fasman

FASTA format
Accession number Genbank Identifier Protein designation

>gi|66734543|gb|AAY53629.1| my invention MANYTIMESTHEREISASLAPDASHTENDENCYHERE WASTINGFEMALESTIMESANDGENTLEMENSSANITY SINCETHEYAREINSANEANDWARLIKEWITHLITTLES ENSEATALL

> Important in FASTA format. 1st line deleted for non-FASTA format