Ls3 - Lecture 3

Primary

Secondary

Tertiary

Quaternary

Primary Structure. Just an unfolded amino acid sequence

Secondary Structure. Secondary structure refers to regularly repeating elements within a protein, in which hydrogen bonds form between polar atoms in the backbone chain.Local structure (alpha helix & beta pleated) held together by Hydrogen bonds between the peptide backbone. The portion of a protein that has neither α helices nor β conformation is composed of loops and turns that allow secondary structural elements to reverse direction back and forth to form a folded, globular protein.

Tertiary Structure. 3D structure held together by weak interactions like disulfide bonds. This is the proteins lowest energy state.

Quaternary Structure: Multiple subunits in large complex. Not held together by peptide bonds. Are held together by

- Hydrogen bonds between polar R-groups, Hydrophobic effect between Non-polar R-groups in presence of polar groups,

- Ionic bonds between charged R-groups

- Van der waals between non-polar R-groups

- Covalent: Disulfide bonds

Van Der Waals interaction between non-polar molecules.

Pi Stacking between aromatic molecules (adjacent base pairs in DNA).

Hydrogen bonds in proteins and nucleic acids (polar molecules).

Hydrophobic effect: Tendency of non-polar molecules to exclude water

They form homo/hetero dimers.

A protein consisting of two polypeptide subunits. This is the quaternary structure.

Two copies of the same protein to perform a function.

Two different proteins coming together to perform a function.

Has Hydrogen bonding just between the peptide backbone (unlike DNA double helix which has H bonds in side chains). R groups stick out and are available to interact with other secondary structures. The secondary structure is held together by the hydrogen bonds. The hydrogen in the amide nitrogen forms a hydrogen bond with the carbonyl oxygen, this makers one helical turn.

All the hydrogen bonds of an α helix point in the same direction, and this sets up an electric dipole that gives a partial positive charge to the N-terminus and a partial negative charge to the C-terminus of the helix. Because the last four residues at either end of an α helix are not fully hydrogen-bonded, the dipole charges are spread out on these residues.

- Consecutive stretches of amino acid residues with long or bulky R groups cannot approach one another closely enough to form the tightly packed α helix.

- Also, polar side chains can hydrogen-bond to the peptide backbone, thereby destabilizing the helix.

- Consecutive like-charged R groups repel one another in the close confines of the α helix.

- Proline is infrequent in α helices because its cyclic structure lacks an amide hydrogen-bond donor and restricts N–Cα bond rotation.

Side chains spaced four residues apart are stacked upon one another in the helix. Oppositely charged side chains that are close together can form an ion pair, which stabilizes the helix. Likewise, aromatic side chains with this four-residue spacing can form hydrophobic effects that stabilize the helix. Amino acids with a charge opposite to the partial charge of the helix dipole are sometimes located at the ends of a helix, which adds stability.

Have R groups facing opposite sides. This alternating geometry prevents the interaction of R groups of adjacent residues. Also because of this, one side can be polar or non-polar & provide a shield.

The β sheet, like the α helix, is formed by hydrogen bonds between backbone amide and carbonyl groups, but unlike the α helix, the β sheet structure cannot form from one β strand. Instead, all hydrogen bonds are formed between the backbones of two different β strands.

They are parallel when all sheets have the hydrogen pointing in the same direction. They are anti-parallel if the hydrogen's point in the same direction but shift and alternate. Anti-parallel sheets are more stable because they form nearly straight hydrogen bonds.

Hydrogen bonds between sections of the polypeptide backbone

Lipids are extremely hydrophobic & water is excluded from the lipid bilayer. Polar amino acids wont go through this span. We need a lot of hydrophobic amino acids when spanning through the barrier.

They are particularly stable and common arrangements of multiple secondary structural elements. They are linked together to form sections of domains, or even whole domains. Motifs are made of alpha helix's or beta-pleated sheets.

Helix-turn-helix Motif

Four-Helix Bundle Motif

Coiled-Coil Motif

Helix-Turn-Helix motif. Proline is found in the turn, not in the main structure. Sometimes found in proteins that bind specific DNA sequences

Four-Helix bundle motif

Coiled-Coil motif. Used to bind/grab DNA. Common in DNA & binding proteins. Two α helices pack against each other and gently twist around one another in a left-handed supercoil. The two α helices interact through hydrophobic contacts along the sides of each helix that form the coiled-coil interface.

The size of α helices and β strands is limited by the diameter of a globular protein, and these structures must repeatedly reverse direction back and forth to form a properly folded protein. These are called reverse turns.

The interaction between α helices in a protein occurs through hydrophobic surfaces that face one another.

A) Homodimer

B) Homotrimer

C) Homooligomer (multiple non-identical subunits)

The folding of the many different domains in a single, very large polypeptide chain may be problematic. In addition, if one domain did not fold properly, the entire protein would lack function, so the investment of energy in making it would be wasted. A multi=subunit composition avoids these problems. If a protein subunit misfolds, it will not be included in the oligomer, but at least only the investment of cellular resources to make this one domain will be wasted.If one subunit subsequently denatures (becomes unfolded) or becomes inactive for any reason, it can be replaced by another subunit. The accuracy of translation is also an issue for very large proteins. During protein synthesis, approximately one mistake occurs in every 100,000 peptide-bond joining events. Therefore, a large protein of Mr exceeding 106 may accumulate mistakes, perhaps becoming inactive; smaller, individual subunits that do not fold properly can simply be discarded. Finally, the architecture of many large oligomers includes multiple copies of some subunits. More DNA would be required to encode a single large protein than is needed to encode multiple

Neutral non-polar

On this inside of the protein.

Nonpolar, aromatic, polar, charged. Nonpolar are the best.

Examine

Your hair is a coil of coils. Amino Acids are linked together in hair by disulfide bonds between keratin chains and this gives it strength and structure.

It breaks disulfide bonds between alpha helices so hair shape can change

Anti-Venom are just antibodies to the venom.

Antibodies (immunoglobulin) are proteins produced by the immune system. Antibodies bind antigens very specifically. In some cases, antibodies can distinguish between proteins that differ by a single amino acid.

A foreign substance that elicits production of an antibody.

B cells in the body become plasma cells when they are secreting antibodies. These antibodies are specific for a certain pathogen thats in the body. Scavenging cells in the body look around for things that shouldn't be there. When they find it, they kill it and present pieces of foreign agent on the surface. B-cells will make antibodies specific for this foreign agent to target it for destruction.