Proteins have developed a general connotation in the media and everyday life, especially with nutrition and exercise.  Does the word make you think of a protein shake or a chicken drumstick?  From a cell biologist's point of view, it is the simple idea of putting amino acid monomers together to form a polymer, a protein macromolecule containing certain types of information.

In biology, structure and function always seem to be connected in some way.  Proteins function by binding to similar or different proteins.  They can also interact with other molecules.  This binding requires shapes that will fit the specified target.  As you can see, the three dimensional structure is very important to protein function!  As a matter of fact, a functioning protein is said to be in its native conformation.  However, the loss of native conformation (denaturation) can be induced by HEAT, pH, IONIC CONDITIONS, FREEZE THAWING, AND various CHEMICAL DENATURANTS.  As we discussed earlier, the information in cells are carried in linear sequences.  How do 3-D proteins arise?

A famous experiment by Christian Anfinsen at the NIH in 1956 used mercaptoethanol (CH₃CH₂SH) and urea to break the dissulfide bonds of ribonuclease A.  These enzymes ceased to function properly so denaturation had occurred.  When the two agents had been removed, the molecules resumed normal enzymic activity and returned to the original forms!  The conclusion was that the linear amino acid sequence of a polypeptide contained all the directions needed for 3-D structure.  Of course not all proteins fold quickly enough so chaperones bind to them to speed up the processes.

How do those scientist people figure out the 3-D structure of proteins?  There are different ways to do this, but beware... the functional state may not be the same as the state a protein is in while being examined.

                One experimental approach is NMR spectroscopy.  This will work best with small proteins.

                X-ray diffraction requires a crystalline structure.  A thin beam of X rays of a single wavelength is sent towards a
                crystal, and the scattered radiation allows for complex calculations and analysis.  Then they guess randomly or
                something :) .  Well, I am sure they have the diffraction patterns and spots of different positions and intensities
                figured out so that 3-D structure can be determined.

Let's move into the concepts behind the framework of proteins.  The linear sequence of monomers is held together by peptide bonds.  The loss of water (hydrolysis) accompanies the linking of two monomers.  The reason for the interaction between the carboxyl group and the amino groups is that the new structure will be resonance stabilized.  Note that the peptide bond will not rotate like a single bond because of its resonance structure which will make it a double bond that is sp² hybridized (orgo chem, ugh!).  Only the alpha carbons will rotate.
 
 
 
 
 
 
 

 Here's a gen chem review.  Hydrogen bonds (represented by the striped line in the picture of 2 water molecules) form between an electronegative atom with a lone pair of electrons (like oxygen or nitrogen) and a hydrogen (that is bonded to another electronegative atom).  This occurs because the hydrogen has a very partial positive charge due to its polar covalent bond.  The lone pair of electrons will form a hydrogen bond with the electrophilic proton.  This helps to hold DNA helices together, but they also occur between about every 4 (actually 3.6) residues in an alpha helix protein.  Residue is the term describing amino acids incorporated into a polypeptide chain.

Now here are a few things to note about the alpha helix.
1) The R groups are projected outwards.
2) The side of an alpha helix facing into a polar solvent can project only polar residues while the other side can contain only nonpolar side chains.  This type of protein would be amphipathic (containing both polar and nonpolar characteristics).
3) Stability is increased from the numerous H bonds parallel to the polymer's long axis.

The R groups of amino acids become important at the level of tertiary structure because of interaction between nonadjacent polypeptides.  Relationships between distant monomers, the environment, and proteins create implications.  For example, various amino acids coming out of a ribosome into aqueous solvent will react differently.  Remember amino acids can be polar charged, polar uncharged, or nonpolar.  In fact a DRIVING FORCE OF PROTEIN FOLDING IS TO INTERNALIZE HYDROPHOBIC R-GROUPS.  A variety of noncovalent interactions like ionic/electrostatic bonds, hydrogen bonds, Van der Waals forces, and disulfide bonds (between cysteine sulfhydryl groups) all help proteins to fold to hide these nonpolar sides.  Autonomous folding regions (units) are called domains.  They are parts of a protein that would still look like a full protein if you cut it out of the whole structure.  Examples of DNA binding domains (or structural motifs) include helix-turn-helix, cysteine-histine zinc finger, cysteine-cysteine zinc finger, and leucine zipper.  A mosaic is a multiple domain.

So we've gone from amino acids to polypeptides to folds of protein (polypeptides) to this.  The quaternary structure of proteins can be determinate or indeterminate (i.e., it is hard to say where individual units of actin muscle filaments start and stop.)  The subunits are held together by noncovalent interactions (remember the disulfide bonds?)  This creates multiple protein complexes.

Another point is that binding is often determined by only a small number of amino acids.  For example, millions of immunoglobulins have the same overall structure, but there are millions of different specific binding activities.  The reason: there are sequence differences in their 6 small surface loops.