Researchers at UCLA have designed a hollow, pyramid-shaped protein with a controllable cavity size that may aid the capture and release of smaller compounds. The tools used in this work, including small angle X-ray scattering techniques at the SIBYLS beamline in the Advanced Light Source (ALS), will help analyze and optimize designed-protein assemblies and understand their behavior in solution. Read more in the ALS Science Brief.
Cyclic proteins that assemble from multiple identical subunits (homo-oligomers) play key roles in many biological processes, including enzymatic catalysis and function and cell signaling. Researchers in the Molecular Biophysics and Integrated Bioimaging (MBIB) Division worked with University of Washington’s David Baker, who led a team to design in silico and crystallize self-assembling cyclic homo-oligomer proteins.
University of Washington (UW) researchers have designed a novel protein with properties that could lead to the generation of new photoactive proteins. This three-fold symmetric, self-assembling protein homotrimer contains a highly stable noncanonical amino acid. Noncanonical amino acids are not found among the 20 encoded amino acids in the body and can contain modifications to allow for new functionality. In this case, this amino acid contains a bipyridine group that chelates metal, thereby introducing new photochemical properties into the protein interface, and nucleating the formation of the homotrimer.
An article published last month in PNAS describes this work from a team of scientists led by David Baker at UW, which included Jose Henrique Pereira, Banumathi Sankaran, and Peter Zwart of the Molecular Biophysics & Integrated Bioimaging Division (MBIB). The MBIB scientists developed the crystal screen that was used to crystallize the novel protein and performed X-ray crystallography on Beamline 8.2.1 in the Berkeley Center for Structural Biology at the Advanced Light Source. Their X-ray crystallographic analysis of the homotrimer showed that the design process had near-atomic-level accuracy, demonstrating that computational protein design together with the utilization of noncanonical amino acids could be used to generate novel protein functions. These methods could be used to develop new therapeutics, biomaterials, and metalloproteins with useful optical or photochemical properties.
Calcium channel blockers are widely prescribed for heart and blood-vessel diseases. With the help of the high-intensity x-ray beams and remotely controlled robots at the Advanced Light Source (ALS), two groups of scientists from University of Washington have revealed, at atomic resolution, how two different classes of calcium channel blocker drugs produce their therapeutic effects. The researchers took advantage of the remotely controllable robot automounter available in the Berkeley Center for Structural Biology at the ALS to screen a large number of crystals for the best diffraction. The tunable x-ray source also allowed them to collect anomalous diffraction data at Beamlines 8.2.1 and 8.2.2 with bromine-incorporated drugs, which was critical for locating the drug molecules in the crystal. The results pave the way for optimizing these classic compounds for safer and more reliable pharmaceutical applications. Read the ALS Science Highlight.
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.