Molecular Biophysics and Integrated Bioimaging (MBIB) Division scientists led by Eva Nogales have resolved the 3-D structure of a critical human cellular protein complex involved in DNA transcription and repair at an unprecedented level of resolution. The complex, called transcription factor IIH (TFIIH), unzips the DNA double helix so that genes can be accessed and read. Malfunctions of the complex are associated with premature aging, cancer propensity, and a variety of other defects. One challenge with solving the structure of TFIIH has been that it exists in such minute amounts that it is difficult to produce and purify in large quantities. Moreover, once obtained, it may not form crystals suitable for X-ray diffraction. The researchers used cryo-electron microscopy (cryo-EM), a technique in which purified samples are flash-frozen at ultra cold temperatures, and which works even on very small quantities. “The fact that we resolved this protein structure from human cells makes this even more relevant to disease research,” said Nogales. Basil Greber, a postdoctoral fellow in Nogales’s lab, was first author on the study published in the journal Nature. Computational research scientist Pavel Afonine and MBIB Division Director Paul Adams also contributed to the project. Read more from the Berkeley Lab News Center.
Amy Herr is one of three recipients of the Berkeley Chamber of Commerce’s Visionary of the Year award for 2017. The honor is bestowed annually to local innovators tackling real-world challenges with “imagination and persistence.” Herr is a professor of bioengineering at UC Berkeley and a Berkeley Lab Biosciences Area faculty engineer with a primary appointment in Biological Systems and Engineering (BSE) and a secondary appointment in Molecular Biophysics and Integrated Bioimaging (MBIB). Her research focus is on inventing tools to analyze the levels of various proteins within single cells, which has applications for the treatment of diseases such as cancer. Read more from UC Berkeley News.
A team of Berkeley Lab researchers conducted X-ray footprinting mass spectrometry (XFMS) experiments at the Lab’s Advanced Light Source (ALS) to pinpoint how a protein of the bacterium Shewanella oneidensis transfers electrons to a metal oxide substrate. The research was led by Caroline Ajo-Franklin, whose lab is part of the Molecular Foundry and who holds a secondary appointment in the Molecular Biophysics and Integrated Bioimaging (MBIB) division, in collaboration with Corie Ralston, also of MBIB. Tatsuya Fukushima, a former postdoc in Ajo-Franklin’s lab, and Sayan Gupta, a member of Ralston’s lab, were co-first authors on the paper published in the Journal of the American Chemical Society. The study, which identified an unexpectedly small and weak binding site, also benefitted from expertise and tools contributed by Joint BioEnergy Institute (JBEI) and Biological Systems and Engineering (BSE) researchers Christopher Petzold and Leanne Jade Chan. Read more at the Berkeley Lab News Center.
Molecular Biophysics & Integrated Bioimaging (MBIB) Division scientists Aaron Brewster, Nicholas Sauter, and James Fraser were part of an international team led by William DeGrado at UCSF that used an X-ray free-electron laser (XFEL) source to visualize the arrangement of water molecules inside the influenza matrix 2 (M2) channel at room temperature. The M2 channel of influenza A is essential for the reproduction of the flu virus, making it a target for therapeutics, and it is also a model system for studying how protons are transported across a membrane bilayer. The XFEL method overcomes the limitations of previous crystallographic structures obtained using synchrotron radiation with cryocooling. While cryocooling helps to preserve crystals against rapid radiation damage, it imparts an artificially higher degree of order of the water molecules than structures obtained near room temperature. By using room temperature XFEL to study the M2 channel at various pH conditions, the researchers have gained a more accurate picture of the behavior of water molecules and their role in proton transport in these channels. The study was published in the Proceedings of the National Academy of Sciences.
While studying chemical reactions of a gold-containing molecule, Berkeley Lab researchers led by Jim O’Neil in the Molecular Biophysics and Integrated Bioimaging (MBIB) division and Dean Toste in the Chemical Sciences division happened upon a chemical mechanism that can be used to form trifluoromethyl (CF3) compounds and attach them to other chemical compounds. Mark Levin, who participated in the study as a UC Berkeley graduate student working with O’Neil at the Biomedical Isotope Facility at Berkeley Lab, was first author on the study published in Science. The discovery could aid in the synthesis of new radiotracers for use with the 3-D medical imaging technology known as positron emission tomography (PET). Read more from the Berkeley Lab News Center.