As Nobel Laureate Johann Deisenhofer once put it: "Genes alone can do nothing. Life comes with proteins."
And he's indeed right: Proteins are an essential ingredient of each and every cell and constitute most of its dry mass.
These macromolecules are prerequisite for life on earth: Proteins can be found as hormones.
A very famous one is insulin which is essential for the regulation of the glucose metabolism.
As enzymes, for example lactase, proteins can also catalyze biochemical reactions, or work as transport vehicles like hemoglobin.
Often they are found as embedded parts of biological membranes.
Moreover proteins are involved in cell signaling and communication,
protect us as antibodies and help cells to maintain its structure.
The entire set of expressed proteins in a cell, a tissue or an organism is called the proteome.
With hindsight we now know that Swedish chemist Jöns Jacob Berzelius was spot on when in the 1830s,
he picked the name for these macromolecules.
It is derived from the Greek word "proteios", which means "standing in front" or "in the lead".
Although proteins are capable of doing almost everything, as Nobel Laureate and biochemist Francis Crick once said,
every protein is unique among thousands of others.
This is chiefly due to its chemical structure: Every protein consists of a determined set of different amino acids.
Some proteins consist of only 50 to 100 acids, others contain hundreds or even thousands.
The amino acid sequence of proteins is encoded in the deoxyribonucleic acid,
which lays the foundation for the "central dogma of molecular biology": DNA leads to RNA leads to proteins.
Via an amino-group and a carboxyl-group, which all amino acids have in common,
two of them can form a very strong type of chemical bond - the so called peptide bond.
Through this chemical reaction amino acids can build long chains, similar to a necklace.
In living cells this process of protein synthesis is called translation.
It takes place in small granular components within the cytosol, which today are known as ribosomes.
The amino-acid-sequence of a protein is called its "primary structure" and forms the protein's "backbone".
But this marks only a starting point:
To achieve their ultimate function within an organism, proteins need to fold up into their unique, three-dimensional structure,
which represents the thermodynamically most stable conformation of lowest energy in the intracellular environment.
After the primary structure or the necklace is built up,
the amino-acid-chain begins to fold up into its so-called secondary structure.
The most common examples for these structures are known as alpha-helix and beta-sheet which can form loops.
All of them are stabilized through non-covalent hydrogen bonds.
But the stepwise production of a protein is still not finished:
Since every amino acid has its own characteristic side chain,
an electrostatic interplay between the alpha-helices, beta-sheets and loops occurs:
Hydrophobic interactions develop which finally lead to the specific,
three-dimensional native conformation of a protein - the necklace gets folded.
This is known as the tertiary structure and is also stabilized through salt-bridges and disulfide-bonds.
The first protein whose three-dimensional structure was determined was myoglobin - the carrier of oxygen in muscle-cells.
John Kendrew was able to determine its structure via X-ray crystallography in 1958, he won a Nobel Prize for this work in 1962.
And finally, there's also the so-called quaternary structure
which occurs when several protein-subunits form one big protein complex.
Over the years much progress has been made in the field of protein-folding.
Nowadays, molecular modeling is one common way to predict the three-dimensional structure of a protein,
because often it is very difficult or too difficult to gain high amounts of native protein in vitro.
Computer modeling is based on sequence analysis and comparison with already well-characterized, phylogenetic similar proteins.
This technique enables the simulation of a protein's spatial structure.
But in the end, a simulation is merely a "could be" - it will never be as exact as an empirical characterization of a protein.
Johann Deisenhofer 2010:
AND MODELING IS CERTAINLY NOT YET PRECISE ENOUGH TO EXPLAIN CHEMISTRY.
SO EVEN IF YOU CAN DO HOMOLOGY MODELING OF A PROTEIN WE SO FAR CANNOT COME CLOSE ENOUGH
TO THE REAL STRUCTURE TO EXPLAIN THE CHEMISTRY OF, LET'S SAY, AN ENZYMATIC REACTION.
Every day, scientists correspond and exchange their latest results through a worldwide database called Protein Data Bank or PDB.
As of now, structural information of around 91,000 proteins can be found via this platform.
Yet it remains a big mystery how a protein can find its native conformation within less than a second while in theory,
it would need many billions of years to try all its conformational possibilities.
Even today, the native conformation of a protein cannot be exactly predicted solely on the basis of its amino acid sequence.
Christian Anfinsen 1983:
THE WHOLE PROBLEM REACHED THE POINT WHERE IT BECAME IMPORTANT TO DECIDE: WHY DID THIS HAPPEN?
IT WAS OBVIOUSLY A THERMODYNAMIC EVENT AND ALWAYS WENT THE SAME WAY.
WHY DID THIS HAPPEN?
WHAT COULD ONE REDUCE FROM THE STRUCTURE OF A PROTEIN, THE POLYPEPTIDE SEQUENCE AND SO ON,
THAT WOULD TELL SOMETHING ABOUT THE MECHANISM BY WHICH THIS FOLDING OCCURRED.
AND THAT'S STILL AN EXTREME POPULAR PROBLEM.
The situation is complicated by the fact that proteins undergo different kinds of so called post-translational modifications
after having left a ribosome.
They are essential for intracellular regulation.
For example, one third of the many thousand different proteins, that are active in an average mammalian cell,
are phosphorylated at any given time:
A phosphate group is attached to them for reasons of intercellular communication.
Switching proteins involved in signaling cascades either "on" or "off".
But there are also other mechanisms of regulation, which do not always switch on a protein, but sometimes initiate its death.
It was long thought that polypeptide chains are rock stable and live as long as we do -
until in 1941 biochemist Rudolf Schönheimer suggested the idea of proteins as dynamic structures.
It took some decades to confirm his idea, but finally this was done by Aaron Ciechanover and Avram Hershko.
They discovered the ubiquitin-proteasome pathway as the major way of protein degradation in the cytosol of eukaryotes.
Together with Irwin Rose the duo received the 2004 Nobel Prize in Chemistry for their discovery:
In an enzyme-cascade a polyubiquitin-chain is added to a misfolded, unneeded or foreign protein.
Once marked in this way, the protein is recognized by the proteasome, a cylindrical protein-complex,
which is abundant in the cytosol.
Inside the proteasome, ubiquitin-tagged proteins are degraded into peptides,
which then can be further degraded into shorter amino-acids.
These mechanisms are indispensable to life, since protein degradation is essential in cellular processes
such as the cell cycle or gene expression and also functions as a quality control.
So one could conclude: Life is only possible with death - even in the case of proteins.