THE RIBOSOME—THE FACTORY FOR PROTEIN PRODUCTION ACCORDING TO THE GENETIC CODE

synthesized


FROM DNA TO PROTEINS
Each living cell contains a genetic code, which is the instructions for the creation of the cell components and the entire living organism.This substance is inherited from parents to their o spring.The genetic material is called DNA and can be considered a cookbook that DNA The genetic material passed from parents to their o spring.It contains the instructions to produce the cell components, called genes.DNA consists of four building blocks called nucleic acids.contains all the information necessary for the creation and functioning of the living organism.One of the most important components of DNA are genes, which contain instructions for the synthesis of the proteins-the "machinery" of the cells and of the entire living body.

PROTEINS
The "workers" of the cell-molecules that perform most actions in the cell, and in the body in general.These include, for example, producing movement (muscle activation), transporting oxygen and removing carbon dioxide from the blood (respiration), building the body's skin and connective tissues (structure), and protecting the body from invaders (immune system).
Proteins perform many actions that are important for the functioning of the body.
All natural proteins consist of a combination of about building blocks called amino acids.To form a protein, the amino acids are

AMINO ACIDS
The building blocks of proteins.There are about di erent amino acids.Within the proteins, the amino acids are linked together by a peptide bond.These bonds connect the amino acids into chains, and this is how the protein is formed.An average sized protein consists of amino acids.joined together like beads on a chain.This connection is called a peptide bond, and a medium-sized protein contains between

PEPTIDE BOND
The chemical bond that links amino acids together in a protein.
and amino acids linked together.Each such long chain of amino acids folds into a unique, functional three-dimensional structure determined by the sequence of the amino acids that make it up.The protein structure is precisely tailored to execute the function that the protein is intended to perform (Figure ).An mRNA molecule is a "copy" of the genetic information that allows the genetic material to be transferred inside the cell without "endangering" the original code.In the next stage, the mRNA reaches the ribosome, the cell's "factory" for protein production.The ribosome "reads" the instructions from the mRNA and prepares the desired protein by forming a chain of amino acids joined to each other by peptide bonds.After exiting from the ribosome, the protein chains are folded into the proper three-dimensional structure required for the protein to function.This process of protein production in the ribosome is called translation.The rest of this article will focus on how the translation process occurs in the ribosome.

THE RIBOSOME
The translation of a new protein is a complicated process.The "recipe" for proteins is encoded in the genetic code (DNA and mRNA), in a genetic "language" of four letters that is translated into a "language" of amino acids that contains about di erent building blocks-the amino acids.You are probably wondering, "How is this possible?"The process is called translation, and the name suggests the process.The solution to this problem is that the ribosome reads the genetic code as a series of three-letter combinations of nucleotides called codons.Each codon corresponds to a particular amino acid (some amino acids have more than one codon.Sometimes there are up to four di erent codons that are translated into the same amino acid) or a stop signal.The ribosome is responsible for the translation, namely creates the connections between the amino acids into the nascent protein.
The ribosome is a cellular organelle composed of two subunits: the small ribosomal subunit and the large ribosomal subunit (Figure ), each of which has a specific function.The small ribosomal subunit is responsible for reading the genetic code from the mRNA and matches between the bound mRNA codon and the corresponding anticodon on the transfer RNA (tRNA).The site where the genetic code is read is called the decoding center.The large ribosomal subunit is responsible for catalyzing the new peptide bond between the amino acids and Yonath et al.
The Ribosome for passing the synthesized protein through the ribosome into the structure of the protein (right).This unique structure is appropriate for the function of the protein produced (one of the many di erent functions of the various proteins in the body).Image adapted from here.
Nascent Peptide Exit Tunnel (NPET).In the catalytic center of the ribosome, the peptidyl transferase center (PTC), the amino acids bind to each other, and a new peptide bond is formed.The PTC allows the bonding of the two amino acids as within it, they are situated in close proximity and in the proper orientation to create a new peptide bond.After the new bond is formed, the tRNA holding the nascent protein moves together with the mRNA to the "next station" across the ribosome, ready to form a new peptide bond.The nascent protein chain passes through the large ribosomal subunit within the NPET and emerges at the other end of the ribosome.The small and large ribosomal subunits are bound to each other during

MESSENGER RNA (mRNA)
A type of RNA that copies the genetic information from DNA to the ribosome, where it serves as a template for protein synthesis.During the process of protein assembly and detach from each other when protein translation is complete.Each ribosomal subunit consists of proteins and very long RNA chains called ribosomal RNA (rRNA) (Figure ) [ ].There are many ribosomes in each living cell-from tens of thousands in bacteria, for example, to millions in human cells.The work of ribosomes requires a lot of energy-more than % of the total energy used by the cell [ ]!This highlights the importance of the ribosome within the cell, as it is the factory that produces the proteins required for all cellular activities.The ribosome works at an amazing speed: a bacterial ribosome can produce a protein of average size within a few seconds to a minute.
Ribosome translation of an mRNA molecule occurs in three stages: Initiation, Elongation, and Termination: during initiation, an mRNA binds to the small ribosomal subunit of the ribosome.Then a tRNA carrying the amino acid methionine binds to the start codon of the mRNA sequence.The start codon in all mRNA molecules has the sequence AUG, which codes for methionine.Initiation factors join the small ribosomal subunit, mRNA, and tRNA complex, and the initiation complex is formed.Next, the large ribosomal subunit binds and forms the translation complex, i.e., the active ribosome.During the elongation stage, the ribosome translates every codon in turn.For ribosome and carries the amino acid with it.As the ribosome moves across the mRNA, new tRNA molecules loaded with the corresponding amino acid keep binding and moving between the three active sites of the ribosome: the Aminoacyl site (A site), Peptidyl site (P site), and the Exit site (E site) (Figure ).Then the next tRNA carries an amino acid, enters the ribosome, binds to the A site, a peptide bond is being formed between the amino acids bound to the A site and the P site, and the nascent protein chain moves on within the NPET.
Later, the tRNA from the P site moves to the E site and is released from the ribosome.The tRNA from the A site moves to the P site, and a new tRNA binds to the A site.Each time a new amino acid arrives, it binds to the previous amino acid by a peptide bond.In this way, the nascent protein chain is formed [ ].The growing peptide chain passes through the ribosome through a Nascent Peptide Exit Tunnel (NPET) and emerges from the ribosome.Elongation continues as long as the mRNA advances in the ribosome and presents new codons.Termination occurs when the ribosome reaches a stop codon.
A stop codon is a codon on the mRNA for which there are no tRNA molecules that can recognize it.When the translation is complete, the two subunits of the ribosome are separated and the nascent protein exits and folds into its three-dimensional structure, alone or with helpers (chaperones).In this way, the new protein is released from the ribosome and can perform its function in the cell (a video describing this process, can be found here).How did we discover the structure of the ribosome?We developed a unique method to do this, which we will discuss in the next section.

CRYSTALLOGRAPHY INSPIRED BY POLAR BEARS
We have deciphered the structure and function of the ribosome using a method called Crystallography.This method enables us to study internal symmetry that repeat in space in an orderly fashion.The simplest and smallest repeating unit in a crystal is called a "unit cell".
A unit cell of table salt is shown in   Deciphering the structure of a crystal using crystallography.(A) An example of the atomic arrangement in a crystal known from our daily lives-table salt.Table salt consists of two ions: sodium cation (a positive ion-in green) and chloride anion (a negative ion-in blue), arranged periodically in unit cells that repeat in all directions of space.(B) Determining the structure of a crystal using crystallography: the crystal is irradiated with a uniform and concentrated X-ray beam.Due to the arrangement of the atoms that make up the crystal, the X-ray beam is di racted after hitting the crystal.During the experiment, the crystal is irradiated from several angles, and the strength and position of the dots of the image appearing on the screen are measured (right).Using the image of the di racted beam, we can decipher the three-dimensional structure of the crystal.
The first requirement for deciphering structure using X-rays is the preparation of crystals.Some materials, such as sugar, table salt and quartz stone, are natural crystals-these crystals are stable and solid.But most materials and structures in nature and in the body, such as proteins (e.g., hemoglobin) or their complexes, like ribosomes, are not naturally crystallized.Therefore, the first challenge in our research was to find conditions to crystallize the multi-components complicated and flexible ribosomes-a task previously considered impossible, since many famous scientists had already tried and failed.For a long time, we could not crystallize ribosomes because of their extremely complicated structure.Due to their functional requirements in the body, they have motor abilities-and tend to disassemble outside the cell, making their crystallization even more di cult.
One of the many important breakthroughs we made while trying to

TRANSCRIPTION
The process by which a messenger RNA molecule is created based on the DNA molecule.DNA contains all the operating instructions for the production of proteins in the cell (the genes).Since DNA is the original copy and crystallize the ribosome was inspired by polar bears.It turned out that during their winter hibernation, a large portion of the bears' ribosomes are maintained in a dense, almost periodic structure throughout the winter, until the bears awaken from their sleep in the spring.We assumed that this happens so that the bears' ribosomes do not fall function in the spring.This told us that, under stress or extreme conditions, the ribosomes tend to arrange in an almost periodic density, and therefore we chose to produce crystals from ribosomes of bacteria living under extreme stress conditions in the dead sea.Indeed, through intense work and after trying countless di erent conditions, we managed to get stable crystals of active ribosomes.

RIBOSOME
The organelle in the cell that produces proteins.The ribosome consists of two subunits, the small ribosomal subunit, and the large ribosomal subunit.Both subunits are composed of many ribosomal proteins and ribosomal RNA.The small ribosomal subunit is responsible for decoding the genetic code according to the messenger RNA, while the large ribosomal subunit is responsible for protein production according to the instructions of the genetic material.

TRANSLATION
This is the second phase of protein synthesis, in which the genetic information encoded in messenger RNA is used to assemble a chain of amino acids by the ribosome.As the amino acids are added to the growing chain, the protein begins to advance within its tunnel toward exiting the ribosome and folding into its final three-dimensional structure.
After producing the crystals, we knew we would face another di culty.The X-ray beam that we had to use to decipher the structure of the ribosome was of very high energy (produced in giant accelerators, e.g., un Grenoble, Stanford or APS) that a ects the chemical bonds between the atoms of the ribosome crystals and causes migrating atoms.This means that as we irradiate the crystal to collect data about its structure, we are destroying it.In practice, therefore, we would not be able to measure more than a few percent of the information required to determine the ribosome's structure.We knew we had to find a way to collect enough data from the crystallized ribosome before it was destroyed.Hence, we tried to make crystals that would last longer so that we could make more measurements.We developed a method to reduce the damage from the X-ray radiation by rapidly freezing the crystals at very low temperatures (around − degrees Celsius, by using liquid nitrogen), under conditions that would prevent the formation of ice crystals in the liquid surrounding the crystallized ribosome, aiming at minimizing the ability of the ribosomes atoms to move around after their bonds are broken by the intense beam.By using special solvents mixtures, we developed a procedure, that enabled us to minimize the spread of damage caused by the radiation.That is, measuring the di raction of small areas of cooled crystals, while minimizing the damage during measurements, and avoiding the spread of the broken atoms to all areas of the crystal that had not yet been exposed to the radiation.Using this method and some other experimental procedures developed years earlier at the Weizmann Institute of Science, we succeeded in maintaining the di raction abilities of the ribosome's crystals for a long time, and eventually-after years-also deciphering its structure and understanding how it functions.
Throughout our entire project, many scientists thought it was TRANSFER RNA (tRNA) A family of unique RNA molecules each brings a specific amino acid to the ribosome during translation.Each tRNA is specific for a particular anticodon sequence that binds to a complementary codon on the mRNA and carries the amino acid decoded by the mRNA.
impossible to decipher the structure of the ribosome.Well-known scientists even made fun of us for the substantial challenge we were trying to tackle.But thanks to our determination and creativity, we succeeded to accomplish our mission by constantly searching for "out of the box" solutions.In fact, despite the mistrust of our ability in the scientific world, and the wide contempt for our deep cooling procedure, the entire bio-crystallography adopted it within a few months.Our remarkable success also led to an important medical application, which you will read about in the next section.

FIGHTING FOR HEALTH-HOW TO NEUTRALIZE BACTERIA
As mentioned earlier, the ribosome is a highly important component

RIBOSOMAL RNA (rRNA)
A unique RNA sequence that forms the structural and catalytic core of the ribosome.About two-thirds of the mass of the ribosome is rRNA.The last third of its mass is ribosomal proteins.
of every living cell.When the function of the ribosome is significantly impaired, the cell stops producing proteins and cannot continue to function.This is also true for bacteria.Bacterial ribosomes function similarly to human ribosomes but their structures are slightly, although significantly, di erent from that of human ribosomes.These di erences allow us to use antibiotics that harm the bacteria without wounding the patients taking the antibiotics.
There are several antibiotic families.Natural antibiotics are produced in the field of medicine.But you may have heard that some disease-causing bacteria have developed resistance to certain antibiotics, making them even more dangerous.Understanding the structure and function of the ribosome has allowed us to better understand how di erent antibiotics work and how bacteria have developed resistance mechanisms to them, thus provided ideas of how to the fight against antibiotic resistance.This is an example of how the great perseverance and struggle we have invested over dozens of years in deciphering the structure and function of the ribosome have been justified and have borne fruit.In this context, I would like to share with you some recommendations that I have formulated as a result of this process.

RECOMMENDATION FOR YOUNG MINDS
My main recommendation is to follow your curiosity.If you try to contribute new scientific information to a scientific field you are extremely passionate about, you may face problems in searching for support-especially in the beginning.Some might say you have no chance of success.Others might say that your research is misleading, and they might even claim that you are wasting the public's money.I recommend that you focus on your curiosity-be strong and believe in yourself even if you do not yet achieve the goal you wished for.If you delve deeper into the problem that interests you and its logical basis, you will increase the chances of its solution.My goal was to decipher the structure of the ribosome.Throughout the process, I believed that even if I did not succeed in deciphering the entire structure, I would make significant scientific progress along the way.Even before the structure of the ribosome was deciphered, my research led to the development of new methods in crystallography.These methods led to the solution of tens of thousands of previously unknown structures that helped improve our understanding of many biological processes.
Another aspect I would like to share with you is that the more challenging the path, the greater the satisfaction at its end.So be determined and work to overcome the di culties that stand in your way, trusting that great satisfaction awaits you around the next corner.
CITATION: Yonath A, Breiner Goldshtein E and Segev N ( ) The Ribosome-The Factory for Protein Production According to the Genetic Code.Front.Young Minds : . doi: ./frym. .

CONFLICT OF INTEREST:
NS declared that they were an employee of Frontiers, at the time of submission.This had no impact on the peer review process and the final decision.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
COPYRIGHT © Yonath, Breiner Goldshtein and Segev.This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.No use, distribution or reproduction is permitted which does not comply with these terms.

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Figure The structure of proteins.Proteins are made up of building blocks called amino acids.When the amino acids are joined together, they form a chain called the primary structure of the protein.Each amino

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Figure

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FigureThe structure of the ribosome.The ribosome consists of a few dozen proteins (purple and magenta) and chains of ribosomal RNA (turquoise and gray), organized into two subunits: the small ribosomal subunit (turquoise and purple) and the large ribosomal subunit (magenta and gray).The small subunit contains the site where the genetic material is read, called the decoding center, into which the mRNA molecule enters and in which it binds to the transfer RNA (tRNA) according to the genetic code, represented by three letters (see Figure).The large ribosomal subunit contains a site called the peptidyl transferase center (PTC), where the amino acids, carried by tRNA, bind to each other.The two subunits of the ribosome come together during the assembly of a new protein and are separated at the end of protein assembly (Figure credit: Ada Yonath).
Figure A. Each unit cell in a crystal has a fixed measure of length, height, width, and fixed angles between its feces.In a crystal, the unit cells are arranged periodically in three dimensions, side by side, like floor tiles.In crystallography, the crystal is irradiated with a uniform and very concentrated X-ray beam (FigureB).The atoms presented in each unit cell of the crystal di ract the X-ray beam to a few specific directions, determined by the physical law, called Bragg's law, and their properties and positions, once the X-ray beam hits them.During irradiation, images of the scattering of the beam are captured and collected on a screen (FigureB, screen at right) or detector.Using these di raction patterns by mathematical procedures called Fourier equations, we can decipher the three-dimensional structure of the unit cell.

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Figure

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Figure bacteria as weapons in the "wars" between di erent types of bacteria fighting for the same resources.They damage other bacteria by paralyzing an essential mechanism required for bacterial activity.One of these targets is the ribosome.Although the ribosome is huge compared to the size of the antibiotic, most antibiotics bind and block one of the active ribosomal sites: for example, they inactivate the PTC or block the NPET in the large ribosomal subunit, thus preventing the nascent protein chain growth (Figure)by discontinuing its elongation.Another ribosomal target is to block the movement of mRNA within the small ribosomal subunit.This blockade prevents the mRNA from being properly read, which is necessary for the production of a proper protein.Other antibiotics target the A site of the small ribosomal subunit and prevent the tRNA from binding to the ribosome.When this happens, the amino acid cannot bind to the next amino acid in the chain [ ]. Click here to watch a video demonstrating how antibiotics can disrupt the function of bacterial ribosomes. by