Protein Portraits






         The aesthetic alchemy of life

Week 1

Chains of amino acids

One of the most fundamental aspects of proteins is this: proteins are chains.  The chains adopt extraordinary three dimensional shapes. The scientific details of the 3D shapes remain full of surprises, for while Linus Pauling famously sketched the first clear portrait, new brush strokes are steadily being added by the research community, as recently as the latest published structure on view at the Protein Data Bank.

Protein manufacture

Here’s series of nicely artistic textbook figures illustrating the key aspects of protein manufacture.  They are copied from Dealing with Genes by Berg and Singer, and illustrated by Georg Klatt (their book is sadly out of print and is a real steal if you find it at a used book store).  Note how according to the central dogma of molecular biology, genetic information is first transcribed from DNA chains into messenger RNA chains, and is then translated by ribosomes from messenger RNA chains into protein chains using transfer RNA to bring each newly added amino acid to the growing protein chain.

The Central Dogma. Coding goes in the direction DNA makes RNA makes protein.

The initiation of protein translation is an assembly at the start codon (AUG) of mRNA, tRNA and a ribosome

The process of protein translation continues. The protein chain is elongated until the ribosome reaches a Stop codon.

Amino acids:  Elements of a charm bracelet.

Each protein chain is a linear polymer having two distinct ends (N and C).  The units (the 20 aa’s) are joined by peptide bonds.  The “sequence” of a protein chain is given as the list of amino acids in its chain, from N to C.  The illustration below (also from Berg and Singers textbook) lists the twenty amino acids, complete with their generic amino group and carboxyl group (shaded in gray) and their unique side-chain (shaded in yellow).  The full name and the three-letter abbreviation are given for each amino acid.  Each amino acid is also commonly abbreviated by a single letter.  The only letters of the English language that are not associated with an amino acid are B, J, O, U, X and Z.

Berg and Singer -- Amino acids

The amino acids can be described according to three main chemical characteristics:

  1. Is the side-chain oil-like (hydrophobic)?
  2. Is it wettable by water (hydrophilic)?
  3. Is it positively or negatively charged?

In addition, some of the amino acids play special roles.  For example, a cysteine can form a cross-link with another cysteine.  Glycine is special because it has such a tiny side-chain.  Proline is special because its side-chain is locked into a small ring that restricts flexibility.

Practice exercises

Practice exercise 1:  Jot down the one-letter abbreviation for each amino acid.  Here’s a flashcard quiz to help you memorize the amino acid abbreviations.

Practice exercise 2: The following is a numbered list of the twenty side-chains.  Can you assign each number with the name of the amino acid?

twenty_side-chains

Protein folding:  Chains adopt three-dimensional shapes

Protein chains wind around in a 3-D arrangement that is dictated by the character of the amino acids.  As the amino acids interact, they enforce this shaping of the chain.  We call this process “protein folding”.  The final shape that is adopted by the protein is generally very complicated.  Protein scientists use all kinds of specialized nomenclature to describe the resulting “protein fold”.

  • Protein chains often make abrupt turns called “hairpin turns”.  Less abrupt turns are also common.  Turns allow a protein to fold back upon itself so that we end up with something with a complicated three-dimensional shape.
  • A few types of regular “secondary” structures crop up again and again (alpha helices, beta strands).  Various sorts of weak interactions (such as hydrogen bonds) add up to help stabilize such secondary structures.
  • Multiple chains can pack together to give “multimeric” proteins.  A myoglobin molecule, for example, has but one chain.  A single hemoglobin molecule has four.  Fibrous proteins (keratin, silk and collagen, for example) are built of many many chains wound together in specialized registries.

Take a deep breath.  There’s much more … And that is where artwork (and computer graphics) can really help.  A good place to tiptoe into computerized display of protein molecules is at PDB-101.

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