For the 12 Days of “The STEM Chicksmas” we’re highlighting 12 scientists who have contributed something innovative and exciting to their field. It is the season of giving, and these brilliant minds have given incredible gifts to the scientific community! This year we’re looking at 12 Nobel Prize winners from the past 15 years in the fields of Physics, Chemistry, and Physiology or Medicine.
Day Twelve: The 2009 Nobel Prize in Chemistry.
Form follows function—or maybe it’s the other way around. Either way, one of the biggest keys to truly understanding the function of a molecule lies in understanding the atoms that make it up. For this reason, it has been a subject of great interest to find the underlying chemistry of various biological structures, like proteins. One way of doing this is by x-ray crystallography, a technique that uses the diffraction of x-rays to make a picture of the location of all the atoms in a structure. The problem, of course, lies in the size of biological structures. Unlike small molecules, which might contain only a few atoms (water has 3, for example), biological structures contain thousands. Mapping every single one of these atoms is no easy feat—yet the winners of the 2009 Nobel Prize in Chemistry, Venkataraman Ramakrishnan, Thomas A. Steitz, and Ada Yonath manage to succeed in mapping the structure of the ribosome.
Ribosomes are important in the process of encrypting new proteins with genetic information. The attach nucleic acids in the order specified by messenger RNA (to read more about the role of mRNA check out our post here). The ribosome binds to the mRNA, which carries a genetic template, and amino acids are carried to the ribosome by another type of RNA, transfer RNA. The ribosome then links together the amino acids to make a protein! It is an extremely complicated structure with two subunits: in humans the small subunit is made of one RNA molecule and 32 proteins, and the large subunit is made of 3 RNA molecules and 46 proteins. This adds up to hundreds of thousands of atoms….but in the 1970s Yonath decided to map them using x-ray crystallography.
X-ray crystallography is a method to determine the structure of a crystal (read more on our post about quasicrystals here). However, to do x-ray crystallography, the structure has to be crystalline…but most biological structures are aqueous and do not easily crystallize and often fall apart in non in vivo conditions. This was the first of the many problems biochemists faced. It took Yonath 20 years to make a crystal that was of good enough quality to make a clean diffraction pattern.
There arose a new problem: x-ray crystallography yields a diffraction pattern, which is a pattern of dots that yield information about the placement of the atoms. However, to correctly interpret these dots, their “phase angle” had to be determined. Because ribosomes were too large for the normal trick of determining phase angles to be utilized (attaching heavy atoms to the composite atoms), a new method had to be devised. In came Steitz, who used electron microscopy to find the orientation of the ribosomes in the crystals. This helped solve the phase angle problem. With Steitz’s help and Yonath’s years of hard work, the three scientists published good crystal structures of the ribosome within a few months of each other in the year 2000.
These structures were crucial for fully understanding the function of the ribosome. Ramakrishnan discovered nucleotides on the small subunit that measure the distance between structures on the mRNA and the transfer RNA, which helps prevents errors in transferring information. Steitz helped pinpoint atoms that are important in the ribosome’s chemical reactions and in explaining how those reactions occur. These three scientists’ years of hard work explained the structure of the ribosome, and they also contributed to our ability to find the structure for biological molecules. The strides they’ve made, in both form and function, have truly been a gift to our scientific knowledge.
To learn more, check out the Nobel Prize website or the award winning work here (Ramakrishnan), here (Yonath), or here (Steitz)