FOUR LEVELS OF PROTEIN STRUCTURE

condensation reactions

amino acids can undergo ____ in any order, thus making it possible to form large numbers of proteins

primary structure

• the sequence of the amino acids in the chain and the disulfide links.

• linear sequence of amino acids (-P-R-K-F-F-V-G-G-N-W-K-M-N-G-D-K-K-)

• this sequence is determined by the base pair sequence in the DNA used to create it

secondary structure

• structure formed by the way the chain of amino acids folds itself due to intramolecular hydrogen bonding.

  • α-helix

  • β-pleated sheet

  • β-turns loops

supersecondary structure

• associations of secondary structure

• 4 most common motifs:

  • α-α

  • β-hairpin

  • β-α-β

  • greek key helix-loop-helix / motif

domain structure folds or modules

• units of tertiary

  • all alpha, all beta

  • α/β

  • α+β

residue / moiety

each component amino acid

tertiary structure

• complete 3-D conformation

• association of domain structure

  • multidomain (mosaic)

  • single domain

quaternary structure

• association of two or more peptide chains to form protein.

• each polypeptide a subunit

alpha helix

• telephone cord shape is held in place by hydrogen bonds between every N-H group and the oxygen of a C=O group in the next turn of the helix, four amino acids down the chain

• 11 amino acids long

• produces a helical coiling of the peptide backbone such that the R-groups lie on the exterior of the helix and perpendicular to its axis.

A, D, E, I, L, M

amino acids favor the formation of α-helices.

G and P

favor disruption of the helix (producing a bend).

disruption of the helix

important as it introduces additional folding of the polypeptide backbone to allow the formation of globular proteins.

3.6 amino acids

Four carbonyl groups are pointing upwards spaced roughly 100° apart on the circle, corresponding to ______ residues per turn of the helix.

keratin
hemoglobin

proteins in alpha-helix

keratin

fibrous protein whose structure is nearly entirely alpha-helical.

hemoglobin

a globular, flexible molecule whose structure is approximately 80% alpha-helical.

beta pleated sheet

• Composed of 2 or more different regions of stretches of at least 5-10 amino acids.

• Stabilized by H-bonding between amide N’s and carbonyl C’s.

• H-bonding residues are present in adjacently opposed stretches of the polypeptide backbone.

interchain bonds

When the H-bonds are formed between the polypeptide backbones of separate polypeptide chain

intrachain bonds

The H-bonds of a beta-sheet formed by a single polypeptide chain folding back on itself

beta-sheet protein

• Found in both fibrous and globular proteins

• amyloid protein

amyloid protein

• composed of twisted beta-pleated sheet fibrils

• whose 3D structure is identical to that of silk fibrils.

loops

regions that contain residues beyond the minimum number necessary to connect adjacent regions of secondary structure.

turns and bends

• refer to short segments of amino acids that join two units of secondary structure

• (e.g., 2 adjacent strands of antiparallel beta-sheet).

beta turn

• involves 4 aminoacyl residues, in which the 1st residue is H-bonded to the 4th, resulting in a

  180° turn.

• Proline and Glycine are often present

supersecondary structures / folds

• structural motifs

• alpha helix and an antiparallel beta sheet zinc ion is coordinated by two histidine residues and two cysteine residues

Leucine zipper

• bound to DNA.

• The leucine residues are colored red

λ repressor of bacteriophage lambda

employs a helix-turn-helix to bind DNA

amino acid chain in helical, pleated, or random coil form

links itself in places to form the unique twisted or folded shape of the protein

covalent bonding
Hydrogen bonding
salt bridges
hydrophobic / hydrophilic interactions

4 ways in which parts of the amino acid chains interact to stabilize its tertiary shape

covalent bonding

e.g disulfide bridges formed when two cysteine molecules combine in which the –SH groups are oxidized

hydrogen bonding

between polar groups on the side chain.

salt bridges

(ionic bonds) formed between –NH3+ and –COO- groups

functions of domain

• Binding of a substrate or other ligands.

• Anchor a protein to a membrane.

• Interact with a regulatory molecule that modulates its function.

  • Triosephosphate isomerase (beta barrel)

  • HMG-CoA reductase

HMG-CoA reductase

• rate limiting enzyme in cholesterol synthesis in domain structure

• hydroxy methyl glutaryl coenzyme a

globular

These tend to form ball-like structures where hydrophobic parts are towards the center and hydrophilic are towards the edges, which makes them water soluble.

fibrous

proteins form long fibers and mostly consist of repeated sequences of amino acids which are insoluble in water.

hydrophobic interactions

clustering of hydrophobic groups away from water

Charge-Charge
Charge-dipole
Dipole-Dipole

3 types of ELECTROSTATIC FORCES

Charge-Charge

• Favor protein folding.

• Between oppositely charged R-groups such as K or R and D or E.

• (no stopping or pausing)

charge-dipole

Interaction of ionized R-groups of amino acids with the dipole of the water molecule.

dipole-dipole

• The slight dipole moment that exist in the polar R-groups of amino acid also influences their interaction with water.

• Majority of the amino acids found on the exterior surfaces o globular proteins contain charged or polar R-groups.

attractive van der waals

forces involve the interactions among induced dipoles that arise from fluctuations in the charge densities that occur between adjacent uncharged non-bonded atoms.

repulsive van der waals

forces involve the interactions that occur when uncharged non- bonded atomsnon-bonded come very close together but do not induce dipoles.

quaternary structure

• Many proteins are not single strands

• an enzyme having four interwoven amino acid strands.

  • alpha globin

  • beta globin

  • heme

  • Fe2+

oligomeric proteins

• proteins with multiple polypeptide chains;

• can be composed of multiple identical polypeptide chains or multiple distinct polypeptide chains.

homooligomers

proteins with identical sub-units

heterooligomers

proteins containing several distinct polypeptide chains

hemoglobin

• The oxygen carrying protein of the blood.

• contains two alpha and two beta sub-units arranged with a quaternary structure in the form, α2β2

• a heterooligomeric protein