Lecture 4: Proteins and Nucleic Acids Bio Sci 93

Protein

one or more polypeptides folded into a specific 3-D conformation. Functions: support, storage, transport, signaling, receptors, movement, catalysis, defense.

Amino acid

monomer of proteins. Has an amino group, a hydrogen, a carboxyl group, and a variable R group, all attached to the alpha carbon.

Polypeptide

a polymer of amino acids joined in a specific sequence. Ranges from a few to thousands of monomers

R group (side chain)

the variable part of an amino acid. It determines whether the amino acid is nonpolar, polar, or charged.

Nonpolar amino acid

hydrophobic R group (9 of 20). Examples: glycine, alanine, valine, leucine, phenylalanine. Cysteine is weakly polar and sometimes grouped here. R group mostly has C and H

Polar amino acid

hydrophilic, uncharged R group (6 of 20). Examples: serine, threonine, asparagine, glutamine. R group has electronegatives: O, N, or S (e.g., -OH, -NH, -SH)

Charged (ionized) amino acid

hydrophilic R group that is an acid (negative: Asp, Glu) or a base (positive: Lys, Arg, His) at cellular pH (5 of 20). Acids have an extra -COOH in side chain. Bases have an extra nitrogen-containing group in side chain (i.e., -NH2)

Peptide bond

covalent bond joining amino acids, formed by a dehydration reaction (a water molecule is released).

N terminus

amino end: free amino group. amino acid starts with this.

C terminus

carboxy end: free carboxyl group. amino acid ends with this.

Dehydration reaction

joins monomers into a polymer by releasing a water molecule.

Primary structure

the amino acid sequence of a polypeptide. It is determined by the gene (DNA) and drives all higher folding

Secondary structure

local folding from hydrogen bonds between backbone atoms (N-H···O=C). Forms alpha helices (coils) and beta pleated sheets (folds by side). held by backbone hydrogen bonds.

Tertiary structure

overall 3-D shape of one polypeptide, from R group interactions: hydrogen, ionic, hydrophobic, van der Waals (weak) and disulfide bridges (strong, covalent).

Quaternary structure

overall structure from two or more polypeptides combined (an oligomer), stabilized by R group interactions. Examples: collagen (3 helical chains), hemoglobin, transthyretin.

Disulfide bridge

strong covalent bond between the sulfur atoms of two cysteine R groups. Stabilizes tertiary structure.

Denaturation

loss of a protein's conformation caused by changes in pH, high salt concentration, or temperature. Renaturation is refolding.

Chaperone protein

promotes proper folding and refolding by providing the appropriate environment. Found throughout the cell.

Ubiquitin

tag attached to damaged or misfolded proteins, the 'kiss of death.' It marks them for the proteasome.

Proteasome

protein complex that receives ubiquitinated proteins and uses proteases to chop them into short peptides for recycling. Ubiquitin is recycled too.

Proteasome pathway steps

1) Protein tagged with ubiquitin. 2) Enters the proteasome. 3) Degraded into peptides; proteasome and ubiquitin recycled.

Abnormal proteasomal degradation

linked to serious conditions such as cancer, cystic fibrosis, and neurodegenerative diseases.

Sickle cell anemia: cause

single base change in DNA, then single base change in mRNA, then a single amino acid change in the protein (Glu to Val at position 6 of the hemoglobin beta chain).

Sickle cell: effect on hemoglobin

mutant hemoglobin aggregates into fibers, lowering oxygen-carrying capacity and distorting red blood cells into a sickle shape.

Pleiotropic

a single change (e.g., one amino acid in primary structure) can have many different consequences, as in sickle cell: anemia, pain, organ damage, etc.

Multiple myeloma (MM)

cancer of plasma cells (B cells) that build up in bone marrow. They make abnormal, misfolded antibodies and proteins.

Proteasome inhibitors in myeloma

MM cells depend heavily on the proteasome. Inhibiting it (e.g., Carfilzomib, D395) lets misfolded proteins accumulate, triggering apoptosis and killing the cancer cells.

Apoptosis

programmed cell death, engaged when a cell can’t control protein misfolding or damage

Nucleic acid function

store and transmit hereditary information. Two types: DNA and RNA.

Nucleotide

monomer of nucleic acids, made of a pentose sugar, a nitrogen base, and a phosphate group.

Phosphodiester linkage

bond joining the sugar of one nucleotide to the phosphate of the next (a dehydration reaction). Forms the backbone.

Sugar-phosphate backbone

repeating sugar-phosphate units of a polynucleotide. The nitrogen bases project off it as side chains. Strand runs 5' end to 3' end.

Purines

nitrogen bases with two rings: Adenine (A) and Guanine (G)

Pyrimidines

nitrogen bases with one ring: Cytosine (C), Thymine (T, DNA only), Uracil (U, RNA only)

DNA (deoxyribonucleic acid)

double stranded; deoxyribose sugar; bases C, G, A, T.

RNA (ribonucleic acid)

single stranded; ribose sugar; bases C, G, A, U.

Ribose vs deoxyribose

ribose (RNA) has an OH on the 2' carbon. Deoxyribose (DNA) has only H there.

Nucleic aicds

large, essential biomoelcules that store, transmit, and express genetic information in all living cells and viruses