Over the course of billions of years, nature has evolved particular molecular structures that form the basis of life, such as those found in nucleic acids and proteins. Using the natural form as a springboard, University of Washington researchers have designed protein homo-oligomers, or identical interacting subunits, which can contain interchangeable hydrogen bonding modules for building different structures or functions. The team of researchers, led by David Baker at the University of Washington, included Jose Henrique Pereira, Banumathi Sankaran, and Peter Zwart of the Molecular Biophysics & Integrated Bioimaging Division (MBIB).
Researchers at Oregon Health and Sciences University’s Vollum Institute have revealed the molecular structure of the serotonin transporter (SERT), providing new insight into the mechanism of antidepressant action of two widely prescribed selective serotonin reuptake inhibitors (SSRIs) commonly used to treat depression. In their Nature paper, authors Jonathan Coleman, Evan Green, and Eric Gouaux describe their use of X-ray crystallography to capture images of human SERT structures. They collected data at the Beamline 5.0.2 in the Berkeley Center for Structural Biology and used the Phenix software suite to build models and refine the structures. The resulting structures show antidepressants citalopram and paroxetine lock SERT in an outward-open conformation, directly blocking serotonin binding. Visualizing this structure provides a blueprint for future drug design to treat anxiety and depression. This work was highlighted by Nature News and OHSU News.
Naturally occurring proteins—chains of amino acids that fold into functional, three-dimensional shapes—are believed to represent just a small fraction of the universe of all possible permutations of amino-acid sequences and folds. How can we begin to systematically sift through those permutations to find and engineer from scratch (de novo) proteins with the characteristics desired for medical, environmental, and industrial purposes? To address this question, a team led by researchers from the Institute for Protein Design at the University of Washington have published a landmark study that used both protein crystallography (Beamlines 8.2.1 in the Berkeley Center for Structural Biology and 8.3.1) and small-angle x-ray scattering (SAXS; SIBYLS Beamline) at the ALS to validate the computationally designed structures of novel proteins with repeated motifs. The results show that the protein-folding universe is far larger than realized, opening up a wide array of new possibilities for biomolecular engineering. Read the ALS Science Highlight.
Recently, scientists from University of California, San Francisco, performed research at two national laboratories to determine protein structures that c0uld be the key to preventing Ebola infection. Alexander Kintzer and Robert Stroud, used two structural biology beamlines (5.0.2 and 8.3.1) at Berkeley Lab’s Advanced Light Source, to determine in atomic detail how a potential drug molecule fits into and blocks a channel in cell membranes that Ebola and related “filoviruses” need to infect victims’ cells. The study, published March 9 in Nature, marks an important step toward finding a cure for Ebola and other diseases that depend on the channel. Read more at the SLAC News Center.
Aymerick Eudes and Dominique Loqué of the Joint Bioenergy Institute (JBEI) led a study that shows for the first time that an enzyme can be tweaked to reduce lignin in plants. Their technique could help lower the cost of converting biomass into carbon-neutral fuels to power your car and other sustainably developed bio-products. The crystal structure of this enzyme was solved using data collected in the Berkeley Center for Structural Biology at the Advanced Light Source. Read more on the Berkeley Lab News Center.