by Koby Ljunggren
Proteins are much more complex than the number on a nutrient label. They serve as the building blocks for every process that keeps your cells alive. To do this, proteins must be able to mold into many different shapes to carry out their intended function. In every fundamental biology classroom around the globe, students are taught about two major 3D shapes in protein structure: the alpha helix and beta sheet. Officially proposed by Dr. Linus Pauling in 1951, these structures were pivotal in understanding how proteins form and fold into the functional shapes that keep us alive. Later in the twentieth century, this form-to-function relationship pathed the way for a new field of study to emerge known as structural biology. Though Dr. Pauling is often credited with the discovery, one key figure in the lab narrowed the possibilities using his theoretical and mathematical expertise in physics and chemistry. That man was Dr. Herman Branson.
Born in Pocahontas, Virginia in 1914, Branson received his B.S. in Physics from Virginia State College in 1936. Branson then left for the University of Cincinnati to earn a Ph.D. in Physics until 1939. During this time, he took an interest in x-rays, centering his thesis on the interaction and manipulation of these high-energy electromagnetic waves. In 1941, Branson secured an assistant professorship at Howard University, a historically Black university. Branson spent 27 years at Howard, teaching and training the next generation of Black physicists and chemists including figures like Marie M. Daly, the first woman of color to earn a Ph.D. in Chemistry.
The Pauling Lab recruited Branson for his expertise in x-ray analysis and mathematics. Taking a leave of absence from Howard in 1948, Branson worked with Pauling at the California Institute of Technology on emerging discoveries in protein structure. To better understand how proteins are able to carry out their jobs in cells, they sought to fully model the 3D shape of a small protein. By knowing the structure, they hoped to help medical scientists develop drugs that could affect proteins involved in diseases like cancer. In order to determine this 3D shape, the Pauling lab used crystallographic experiments, during which a protein is “crystallized” out of solution, much like a salt. Under the right conditions, a clean, well-ordered crystal may be collected then blasted with x-rays to produce a pattern from which a protein structure may be inferred.
However, proteins are often “blobby” and disordered, making crystallization a difficult, delicate art to this day. And in the 1940s, computer technology did not allow for quick structural determination—many chemists sought a single crystal structure as the basis for their entire Ph.D. The Pauling Lab had some small, simple protein crystals with data that suggested a helical shape, but the lab did not have the expertise to confidently draw this conclusion until Branson arrived to help. Pauling found there was a limited number of possibilities for protein shape—it was Branson’s job to find a structure within those restrictions set by Pauling. Several months later, Branson produced two potential models based off these restrictions: the tightly packed alpha-helix and the looser gamma-helix. After finishing this task, Branson left the Pauling Lab to continue his leave of absence before returning to Howard in the 1950s.
In 1951, the Pauling Lab published a groundbreaking paper in PNAS revealing the alpha helix to be a major and common structure in proteins. Branson was listed as the third co-author on this article. This groundbreaking paper was foundational for protein structural biology, and many folks equated this discovery to the famous proposal of the DNA helix. Indeed, Branson’s work held up to scrutiny, and the alpha helix structure was adopted as the major helical motif model for all proteins.
After Branson’s groundbreaking work on the discovery of the alpha helix, he served as the president of two historically Black universities: Central State University in Ohio and Lincoln University in Pennsylvania. He led efforts to invest in historically Black colleges and universities across the US, eventually helping found the National Association for Equal Opportunity in Higher Education in 1990. After his passing in 1995, Branson is remembered as a groundbreaking scientist and major advocate for higher education.
Koby Ljunggren is a first-year Ph.D. student in the Biophysics Program at Harvard University.
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