Salk Institute for Biological Studies


Senyon  Choe

Senyon Choe

Structural Biology Laboratory



Professor Senyon Choe joined the Salk Institute in 1993 as the first member of the Institute's newly initiated Structural Biology Laboratory. Choe uses X-ray crystallography as a major tool to determine three-dimensional structures of biologically important molecules. He and his colleagues also study the relationship between a molecule's fine structure and the functions it carries out.

Among Choe's recent interests is the study of molecules that bind to specific cells to instruct them to carry out functions. An extension of this work will explore the possibility of designing new molecules that can be delivered specifically to modulate sick cells. His group also has done pioneering work on the molecular structure of an ion channel, important to many physiological functions ranging from heart rate to nerve cell communication.

"Biological messages are written and delivered between cells by messenger molecules in the body. The two messenger systems we are focusing on are called ion channels (for e-mails) and protein hormone receptors (for snail mail). By visualizing these messengers to better understand how such messages are coded for specific delivery, we can create brand-new messages of our own."

The premise that "form follows function" became a mantra for numerous leading architects and industrial designers during a good part of the last century. In biology, evolution operates according to a similar premise because forms with better functionality are likelier to be selected. Trying to understand the relationship between a molecule's fine structure and the functions it carries out, Choe and his colleagues use x-ray crystallography and NMR spectroscopy to zoom in on ion channels and receptors in the cell membrane to visualize how they interact with messenger proteins. Recent work focused on analyzing the three-dimensional structure of a whole protein complex to illustrate how TGF-beta, a messenger molecule that plays a role in cancer, the immune system and heart disease, binds to its receptor molecules on specific target cells to instruct them to do its bidding. An extension of this work explores the possibility of designing new messages to instruct cells to carry out non-natural processes such as coaxing differentiated cells back into an immature, pluripotent state. These types of newly created messages will have tremendous clinical potential as guiding molecules.

Human integral membrane proteins (hIMPs) are attached to the membrane surrounding each cell, serving as gateways for absorbing nutrients, hormones and drugs; removing waste products; and allowing cells to communicate with their environment. Many diseases, including Alzheimer's, heart disease and cancer, have been linked to malfunctioning hIMPs, and many drugs, ranging from aspirin to schizophrenia medications, target these proteins. These receptors and ion channels are extremely hard to produce and hence notoriously difficult to study, but Choe's group recently developed a new technique for rapidly determining their structure. Knowing the exact three-dimensional shape of hIMPs allows drug developers to understand the precise biochemical mechanisms by which current drugs work and to develop new drugs that target the proteins.

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