Lecture 7

proteins

• we are the product of our proteins and protein activity

  • the study of proteins and protein activity: proteomics

• proteins account for most of the dry weight in the cell

• proteins are involved in nearly all categories of cellular function

  • movement (actin/myosin)

  • defense (antibodies, immunoglobulins)

  • structure (keratin)

  • transport (hemoglobin)

  • signaling (glucagon) — not all signaling molecules are lipids

  • catalysis/regulation/metabolism (enzymes)

• most of our (useful) genetic information instructs the cell how to build proteins or regulates that process

• amino acids are the monomers of proteins

  • basic structure of an ionized form amino acid

    • amino (or N) terminus

    • carboxyl (or C) terminus

    • alpha-carbon in the middle

    • side chain, or R-group

  • the R-group (the only part that differs) is what makes one amino acid different from another

• peptide bond formation:

  • amino group seeks out carboxyl group

  • condensation/dehydration reaction

  • resonance helps stabilize

  • H2O lost

• during protein synthesis, ribosomes link amino acids by constructing covalent peptide bonds that join the NH2 (or NH3+) group of the incoming amino acid to the COOH (or COO-) group of what was already there, in the N → C direction

  • the only way ribosomes work:

    • N always attacks C

    • amino group always attached to carboxyl group

    • can only add to C-terminus

  • the ribosomes never go into the rough ER, only the protein does, and rough ER is not the only place that synthesizes proteins

• 20 different amino acids commonly found in proteins

  • differ only in R groups, which confer distinct properties to that amino acid

  • large number of amino acids makes possible a huge number of different amino acid sequences

    • most proteins are >100 amino acids

    • average polypeptides in humans are 250 amino acids

• amino acid R-groups (4 classes based on charge)

  • uncharged, but polar

  • uncharged, nonpolar (hydrophobic)

  • positively-charged (basic)

  • negatively-charged (acidic)

• polar amino acids

  • all have oxygen

  • partial charges can form hydrogen bonds

• nonpolar (hydrophobic amino acids)

  • all side chains are carbon, sulfur, or hydrogen

  • no charged or electro-negative atoms to form hydrogen bonds

• basic (postively-charged) amino acids

  • charged side chains can form ionic and hydrogen bonds

• acidic (negatively-charged) amino acids

  • charged side chains can form ionic and hydrogen bonds

• proteins exist in a virtually infinite number of 3-dimensional conformations

  • that conformation is critical to the functioning of each protein

  • the consequence of folding improperly is usually very significan

    • alzheimer’s, CF, Parkinson’s, Mad Cow — all caused by errors in protein folding → accumulation of toxic insoluble “gunk” (e.g. “plaques” in Alzheimer’s)

• to describe how linear protein chains fold into their 3-D conformations, protein structure is organized into 4 different categories

  • 1° (primary)

  • 2° (secondary)

  • 3° (tertiary)

  • 4° (quaternary)

• primary structure

  • linear sequence of amino acids from N → C

    • which amino acid is in what order

  • all proteins have a unique primary structure

• secondary structure

  • first level of folding

  • stabilized by (relatively weak) hydrogen bonding between 2 different peptide linkages

    • peptide backbone is polar (N-H is partially positive, C=O is partially negative)

  • independent of R groups, so found in most proteins

    • no direct involvement of side chains, literally just peptide bonds

  • alpha-helix and beta-pleated sheets are two major types

    • alpha-helix has about 4 amino acids per turn

  • hydrogen bonds can form between nearby amino and carbonyl groups on the same polypeptide chain