2018 Chancellor’s Award for Postdoctoral Research to DuYoung Min

Duyoung Min, Postdoc in the Bowie lab received the 2018 Chancellor’s Award for Postdoctoral Research. Duyoung developed methods that allowed him to investigate the folding of the most complex proteins ever examined experimentally.

James Bowie was named Fellow of the Biophysical Society

James Bowie was named Fellow of the Biophysical Society and he delivered the Choh Hao Li Memorial Lecture at Academia Sinica.

Other awards:

  • 2018 Choh Hao Li Memorial Lecture, Academia Sinica
  • 2018 UCLA Postdoctoral Society Postdoc Mentoring Award Finalist
  • 2017 Anatrace Award for Membrane Proteins, Biophysical Society

Burroughs-Wellcome Career Award to Calin Plesa

UCLA Chancellor’s Postdoctoral Award, the Burroughs-Wellcome Career Award at the Scientific Interface, has been awarded to Calin Plesa, one of 6 top postdocs to receive of this award. The award is $500,000 to begin his career.

Biochemistry PhD Dissertation Awarded to Yuxi Liu

Graduating PhD student Yuxi Liu from the Yeates lab has been awarded the Biochemistry PhD Dissertation Award from the Department of Chemistry and Biochemistry for her outstanding research accomplishments. Dr. Liu has pioneered the development of designed protein scaffolds that make it possible to image small proteins by cryo-EM. Proteins smaller than about 50 kDa have until now been beyond the scope of cryo-EM methods.

Kristen Holbrook accepted position at Amgen, Toxicology Group

Kristen Holbrook, postdoctoral researcher in Sabeeha Merchant’s group, has recently accepted a position as a Scientist in the Toxicology group at Amgen. Her job will focus on the development and implantation of toxicology strategy for early lead discovery through clinical targets. In addition, she will work with a multidisciplinary team to design and manage a wide array of exploratory and regulatory toxicology studies.

Colleen Hui selected as a Graduate Scholar at LLNL

Third-year Ph.D. student Colleen Hui from Merchant lab has been selected as a Graduate Scholar at Lawrence Livermore National Laboratory (LLNL). Funded by LLNL, the Livermore Graduate Scholar Program allows participants to gain hands-on experience with the cutting-edge instruments available at LLNL, and to apply them toward solving problems in the context of questions that are addressed in their dissertation research. For the next three to four years, Colleen will be working jointly with LLNL staff physicist Dr. Peter Weber and microbiologist/senior scientist Dr. Jennifer Pett-Ridge, as well as other members of Merchant lab, to understand iron homeostasis in the green alga Chlamydomonas reinhardtii. Specifically, Colleen will be using LLNL’s unique nanoscale secondary ion mass spectrometry (nanoSIMS) capability to distinguish the iron storage site in Chlamydomonas cells, and to analyze the dynamics of intracellular iron movement. The outcome of this project will provide a better understanding on trace metal utilization in a model alga for sustainable biofuel production.

HHMI Gilliam Graduate Fellowship Awarded to Jessica Ochoa

Third year graduate student Jessica Ochoa has been awarded a HHMI Gilliam Graduate Fellowship to fund her research and to support her ongoing outreach and diversity activities. Her current research focuses on the structure and function of protein-based microcompartments.

Near-atomic cryo-EM imaging of a small protein displayed on a designed scaffolding system

Significance

New electron microscopy (EM) methods are making it possible to view the structures of large proteins and nucleic acid complexes at atomic detail, but the methods are difficult to apply to molecules smaller than approximately 50 kDa, which is larger than the size of the average protein in the cell. The present work demonstrates that a protein much smaller than that limit can be successfully visualized when it is attached to a large protein scaffold designed to hold 12 copies of the attached protein in symmetric and rigidly defined orientations. The small protein chosen for attachment and visualization can be modified to bind to other diverse proteins, opening a new avenue for imaging cellular proteins by cryo-EM.

Abstract

Current single-particle cryo-electron microscopy (cryo-EM) techniques can produce images of large protein assemblies and macromolecular complexes at atomic level detail without the need for crystal growth. However, proteins of smaller size, typical of those found throughout the cell, are not presently amenable to detailed structural elucidation by cryo-EM. Here we use protein design to create a modular, symmetrical scaffolding system to make protein molecules of typical size suitable for cryo-EM. Using a rigid continuous alpha helical linker, we connect a small 17-kDa protein (DARPin) to a protein subunit that was designed to self-assemble into a cage with cubic symmetry. We show that the resulting construct is amenable to structural analysis by single-particle cryo-EM, allowing us to identify and solve the structure of the attached small protein at near-atomic detail, ranging from 3.5- to 5-Å resolution. The result demonstrates that proteins considerably smaller than the theoretical limit of 50 kDa for cryo-EM can be visualized clearly when arrayed in a rigid fashion on a symmetric designed protein scaffold. Furthermore, because the amino acid sequence of a DARPin can be chosen to confer tight binding to various other protein or nucleic acid molecules, the system provides a future route for imaging diverse macromolecules, potentially broadening the application of cryo-EM to proteins of typical size in the cell.

http://www.pnas.org/content/115/13/3362.long

 

Atomic structures of low-complexity protein segments reveal kinked β sheets that assemble networks

Interactions of LARKS protein domains

More than 1500 human proteins contain long, disordered stretches of “low complexity”—strings of just a few of the 20 common amino acids. The functions of these low-complexity domains have been unclear. Hughes et al. present atomic-resolution structures that suggest that short segments of two such domains can bind weakly to each other by forming a pair of kinked β-sheets. Because aromatic amino acid side chains stabilize these interactions, the interacting motifs are termed LARKS, for low-complexity, aromatic-rich, kinked segments. Numerous proteins associated with membraneless organelles of biological cells contain low-complexity domains housing multiple LARKS.

Abstract

Subcellular membraneless assemblies are a reinvigorated area of study in biology, with spirited scientific discussions on the forces between the low-complexity protein domains within these assemblies. To illuminate these forces, we determined the atomic structures of five segments from protein low-complexity domains associated with membraneless assemblies. Their common structural feature is the stacking of segments into kinked β sheets that pair into protofilaments. Unlike steric zippers of amyloid fibrils, the kinked sheets interact weakly through polar atoms and aromatic side chains. By computationally threading the human proteome on our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, and keratins, which are known to form networks and localize to membraneless assemblies.

 

More information:

http://science.sciencemag.org/content/359/6376/698

Low-complexity domains adhere by reversible amyloid-like interactions between kinked β-sheets

Control of metabolism by compartmentation is a widespread feature of higher cells. Recent studies have focused on dynamic intracellular bodies such as stress granules, P-bodies, nucleoli, and metabolic puncta. These bodies appear as separate phases, some containing reversible, amyloid-like fibrils formed by interactions of low-complexity protein domains. Here we report five atomic structures of segments of low-complexity domains from granule-forming proteins, one determined to 1.1 Å resolution by micro-electron diffraction. Four of these interacting protein segments show common characteristics, all in contrast to pathogenic amyloid: kinked peptide backbones, small surface areas of interaction, and predominate attractions between aromatic side-chains. By computationally threading the human proteome on three of our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such reversible interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, keratins, and cornified envelope proteins, consistent with the capacity of cells to form a wide variety of dynamic intracellular bodies.

https://www.ncbi.nlm.nih.gov/pubmed/29439243