Lub dub, lub dub, lub dub. Every time your heart beats, proteins are creating the electrical current that tells muscles to contract and pump blood through that organ. You may think of proteins simply as food, but protein molecules in the body are responsible for many specialized functions. They are the true workhorses of the cell.
Scientists use NSLS to “look” at proteins, visualizing their structure in three dimensions to learn how they work. For example, discovering protein structures from pathogens such as HIV or tuberculosis can help us understand how drugs interact with them. This can lead to the development of better medicines.
Two remarkable 3D structures describing proteins in the body have been the focus of Nobel Prize-winning research at NSLS.
In 2009, Venki Ramakrishnan and Thomas Steitz, both long-time users of NSLS, won the Nobel Prize in Chemistry for their work on the ribosome. Ramakrishnan, a former employee in Brookhaven’s Biology Department and now at Cambridge University in Britain, and Steitz, Yale University, shared the prize with Ada Yonath, of the Weizmann Institute of Science in Israel.
Present in all living creatures, ribosomes play one of the most important roles for sustaining life - they synthesize all of the different proteins that organisms need to survive every single day.
In the late 1990s, Ramakrishnan and Steitz used x-rays at NSLS to discover the 3D atomic images of two ribosome subunits. They found the structure of these protein subunits - one small and one large - by shooting x-rays into crystals made of these proteins. Protein crystals are notoriously difficult to grow, and it was Yonath who finally figured out how to make crystals of the ribosomal subunits. Her initial work was on bacteria living in the Dead Sea.
Ribosomes are composed primarily of proteins that form a sandwich surrounding ribonucleic acid, or RNA. This RNA center is almost identical across every species on the planet. Antibiotic drugs like streptomycin and tetracycline exploit the differences between bacterial and human ribosomes, killing bacteria by inhibiting their ribosomes while leaving the human ribosomes intact.
In 2001, Steitz and other scientists launched a biotechnology company to exploit their new knowledge of the ribosome. Rib-X, based in New Haven, Connecticut, now has two new antibiotics in human trials and many more in the pipeline. All are aimed at overcoming antibiotic resistance, a growing problem that renders some infections impervious to all known antibiotics.
Depending on your age, activity and physical conditioning, your heart beats anywhere from 50 to 150 times a minute. The beat of a heart - and countless other bodily actions - depends on chemical and electrical signals to relay messages in and out of cells. Proteins called ion channels serve as the conduits for this type of instant messaging.
Ion channels are pores built into the membranes of specialized cells, such as neurons, or nerve cells. Like a tuxedoed guard controlling the velvet ropes on Oscar night, ion channels allow only calcium, chloride, potassium or sodium ions to pass through the cell membrane. They are very selective about who gets in! These ions help generate an electrical current as they cross the pore, and discovering the structure of this channel explained how this protein selects certain ions. (Ions are atoms carrying electrical charges.)
Using powerful x-rays at NSLS, visiting scientist Roderick MacKinnon assembled the first-ever structural details of a potassium ion channel. Potassium ions create the electrical signals that power our hearts and our brains. Gaining insight into how potassium ion channels selectively govern the flow of ions through cells may in the future help us design better drugs for controlling epileptic seizures or steadying the erratic heartbeat of patients with atrial fibrillation.
A Rockefeller University professor and Howard Hughes Medical Institute investigator, MacKinnon shared the 2003 Nobel Prize in Chemistry. His work helps us understand the electrical signaling in the body that underlies all movement, sensation and, perhaps, even thought.