Irina El Khoury

Accelerating the identification of novel secondary metabolites in bioenergy plant root exudates using microcrystal electron diffraction (MicroED)

Lead Institution

Pacific Northwest National Laboratory

Principal Investigator

Vivian Lin

Project type

Cryo-EM Only

Small molecule metabolites drive inter- and intraspecies communication and dependencies in diverse biological systems, yet a large proportion of these important chemical compounds remain…

Cell-free synthesis of Influenza Virus-like particles (VLPs) as prototyping platform for vaccine development and variant characterization

Lead Institution

Environmental Molecular Sciences Laboratory

Principal Investigator

Irina El Khoury

We aim to combine wheat germ cell-free protein expression platform with active microsomes of different origin to synthesize influenza virus-like particles (VLPs). These particles will undergo…

The molecular basis for the role of apolipoprotein A-II in cholesterol and triglyceride metabolism

Lead Institution

Pacific Northwest National Laboratory

Principal Investigator

John Melchior

Project type

Cryo-EM Only

Apolipoprotein (apo)A-II is an abundant human plasma protein primarily in high-density lipoproteins (HDL) but also in very low density lipoproteins (VLDL) and chylomicrons. Despite a large literature…

Accelerating the identification of novel secondary metabolites in bioenergy plant root exudates using microcrystal electron diffraction (MicroED)

Lead Institution

Pacific Northwest National Laboratory

Principal Investigator

Vivian Lin

Small molecule metabolites drive inter- and intraspecies communication and dependencies in diverse biological systems, yet a large proportion of these important chemical compounds remain…

Cryo-EM studies of heteromeric epithelial sodium channels

Lead Institution

Oregon Health & Science University

Principal Investigator

Isabelle Baconguis

Epithelial sodium channels (ENaCs) are members of the ENaC/DEG superfamily of trimeric voltage-independent, Na+-selective and amiloride-sensitive ion channels. ENaCs assemble as heterotrimers that…

Solving the Structure of Eukaryotic Type III Glutamine Synthetase Assembles

Lead Institution

Environmental Molecular Sciences Laboratory

Principal Investigator

James Evans

There are three major classes of the enzyme Glutamine Synthetase (GS) that share widely conserved active-site residues but vary in average protein length, oligomeric assembly state and cofactor…

Cryo-EM studies of DNA damage response proteins

Lead Institution

Mayo Clinic

Principal Investigator

Georges Mer

DNA double-strand breaks (DSBs) are toxic lesions associated with cancer. In chromatin, a complex of DNA and histone proteins that forms nucleosomes, DSBs can be repaired by two different pathways…

Nuclear import of histone H2A-H2B and histone chaperone Nap1 by Kap114

Lead Institution

University of Texas Southwestern Medical Center

Principal Investigator

Yuh Chook

Core histones organize DNA in the nucleus. Histones are synthesized in the cytoplasm and are be transported by to the nucleus by Karyopherin nuclear transport receptors. In the cytoplasm, histones…

Cryo-EM studies of drug transporters

Lead Institution

Duke University

Principal Investigator

Seok-Yong Lee

The SLC superfamily of membrane transporters play critical roles in many aspects of human physiology and pharmacology. Several SLC transporters play roles in drug transport. Of note, nucleoside…

Development of an Integrated Structural Mass Spectrometry Platform for Unveiling the Structure of an Unknown Protein Complex Machinery in Lignin Synthesis

Lead Institution

Environmental Molecular Sciences Laboratory

Principal Investigator

Mowei Zhou

Multiple distinct Lignin-Forming Complexes (LFC) are proposed to be templates and catalysts that orchestrate lignin synthesis in plants. It is hypothesized that each LFC consists of one or more…

Structural basis for recognition of receptor CSPG4 by Clostridium difficile toxin B

Lead Institution

University of California, Irvine

Principal Investigator

Rongsheng Jin

Clostridium difficile (C. diff) is an opportunistic pathogen, which establishes in the colon when the gut microbiota is disrupted by antibiotics or diseases. C. difficile infection (CDI) leads to…

Development of Copper Storage Protein Csp1 as an Electron-Dense “Bio Tag” for Facilitating Structural Determination of Small (< 100 kDa) Proteins by single-particle Cryo EM Methods.

Lead Institution

Oregon Health & Science University

Principal Investigator

David Farrens

Small (< 100 kDa) proteins are challenging to study by standard single-particle cryo-EM techniques, due to their very low signal to noise ratios in images. Heavy atoms could potentially overcome…

COVID19: Structure of COVID19 SARS-CoV-2 Spike protein in complex with monoclonal antibodies.

Lead Institution

Fred Hutchinson Cancer Research Center

Principal Investigator

Marie Pancera

The ongoing global outbreak of atypical pneumonia (COVID-19) is caused by a newly emerged zoonotic beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1). On March 11th,…

Nuclear export of phosphorylated proteins by Karyopherin MSN5

Lead Institution

University of Texas Southwestern Medical Center

Principal Investigator

Yuh Chook

MSN5 is the 142 kDa S. cerevisiae exportin, which exports many different protein cargoes from the nucleus to the cytoplasm in response to cellular environmental changes. Peptide signals in several…

Structure and Function of Adenylyl Cyclase

Lead Institution

Oregon Health & Science University

Principal Investigator

Matt Whorton

Adenylyl cyclases (ACs) are a family of proteins that convert ATP to the second messenger cyclic AMP (cAMP). They are widely expressed and involved in numerous biological processes. The…

Structural Mechanisms of Renal Sensory and Transport Proteins

Lead Institution

University of Utah

Principal Investigator

Erhu Cao

The kidneys regulate blood composition, pressure, and volume, balance electrolytes and acid-base, and reabsorb most salts and nutrients from the initial renal filtrate while excreting metabolic…

Structural basis of synaptic receptor trafficking by PICK1

Lead Institution

University of Pennsylvania

Principal Investigator

Roberto Dominguez

Our goal is to determine the structural-functional mechanism by which the BAR domain protein PICK1 controls the trafficking of synaptic receptors, including AMPA and the dopamine transporter…

Structure and function of the membrane-bound copper-dependent methane monooxygenase in lipid nanodiscs

Lead Institution

Northwestern University

Principal Investigator

Amy Rosenzweig

Particulate methane monooxygenase (pMMO) is the primary enzyme used for methane metabolism by methane-consuming bacteria known as methanotrophs. pMMO is a copper-dependent, membrane-bound…

Structure and function of connexin-46/50 gap junction channels

Lead Institution

Portland State University

Principal Investigator

Steve Reichow

The gap junctions are a class of membrane channel proteins that form direct pathways for cell-to-cell communication. Dynamic mechanisms of channel gating are required to control these communication…

Structure / Function Analysis of Positive-Strand RNA Virus Replication Complexes

Lead Institution

University of Wisconsin, Madison

Principal Investigator

Paul Ahlquist

Positive-strand RNA ((+)RNA) viruses, the largest genetic class of viruses, include numerous major pathogens such as the Zika, MERS, SARS and hepatitis C viruses. A key target for understanding and…

Mechanistic elucidation of inflammasome biology

Lead Institution

Boston Children's Hospital

Principal Investigator

Hao Wu

Innate immunity comprises ancient and evolutionarily conserved biological pathways that are imperative for the recognition of pathogens and endogenous damage. One such major signaling pathway…

Understanding the structural basis of RFX complex in regulating MHC gene expression

Lead Institution

Oregon Health & Science University

Principal Investigator

Liman Zhang

The Major Histocompatibility complex (MHC) is critical in immune system for T cell maturation and self vs nonself discrimination, thus expression of MHC genes has to be tightly regulated. Active…

COVID-19: Structural analysis of SARS-CoV-2 proteins to understand virus immunogenicity and develop therapeutic interventions for COVID19

Lead Institution

La Jolla Institute for Immunology

Principal Investigator

Erica Saphire

Effective and rapid responses to the ongoing COVID-19 pandemic must involve vaccination, therapies and serology. Our laboratory has the required expertise to produce and manage significant volumes of…

Determine the structural basis of splicing modulation by small molecules

Lead Institution

University of Colorado Anschutz Medical Campus

Principal Investigator

Rui Zhao

Aberrant pre-mRNA splicing contributes to 10-15 % of genetic disorders, including Spinal Muscular Atrophy (SMA). SMA is a potentially lethal neurodegenerative disorder caused by loss of function…

KATP channel structures

Lead Institution

Oregon Health & Science University

Principal Investigator

Show-Ling Shyng

ATP-sensitive potassium (KATP) channels couple cell metabolism to membrane excitability and are important for regulating hormone secretion, neuronal activity, vascular tone, and adaptive response to…

Structure of the TRAMP RNA surveillance complex

Lead Institution

Utah State University

Principal Investigator

Sean Johnson

This proposal seeks access to the PNCC cryo-EM facility in order to obtain structural information for the TRAMP (Trf4-Air2-Mtr4 polyadenylation) complex. The goal is to better understand assembly of…

Structural Mechanism of Jordan's Syndrome

Lead Institution

University of Wisconsin, Madison

Principal Investigator

Yongna Xing

Protein phosphatase 2A (PP2A) is an essential and major serine/threonine phosphatase in all eukaryotic cells, and regulates multiple cellular processes and signaling events. Deregulation of PP2A and…

Elucidating the structure of C. elegans TMC1 and TMC2

Lead Institution

Oregon Health & Science University

Principal Investigator

Eric Gouaux

Transmembrane channel-like (TMC) proteins are a unique family of channel-like proteins that are conserved from humans to C. elegans. Vertebrates express eight isoforms, two of which are essential for…

Impact of apolipoprotein E isoforms on brain lipoproteins

Lead Institution

Pacific Northwest National Laboratory

Principal Investigator

John Melchior

Cerebrovascular dysfunction leads to the deposition of amyloid plaques and neurofibrillary tangles in the brain which underlie the development of Alzheimer’s disease (AD); an epidemic that…

Structure and function of the gap junctions

Lead Institution

Portland State University

Principal Investigator

Steve Reichow

The gap junctions are a class of membrane channel proteins that form direct pathways for cell-to-cell communication. Dynamic mechanisms of channel gating are required to control these communication…

Cryo-EM studies of TRP channels

Lead Institution

Duke University

Principal Investigator

Seok-Yong Lee

Transient receptor potential (TRP) channels are a superfamily of calcium-permeable ion channels that are involved in diverse physiological processes. A subset of TRP channels that are known as the…

CryoEM structural determinations of Bacterial Restriction-Modification systems

Lead Institution

Fred Hutchinson Cancer Research Center

Principal Investigator

Betty Shen

Nuclease enzymes are of enormous importance for a wide range of biological and biotechnology disciplines that require site-specific DNA manipulations. Bacterial R-M systems consist of a restriction…

Cryo-EM structural analysis of Glucose-6-phosphatase catalytic subunit, G6PC1

Lead Institution

Vanderbilt University

Principal Investigator

Hassane Mchaourab

The catalytic subunit of glucose-6-phosphatase, G6PC1, functions as a gatekeeper of glucose production in the liver by catalyzing the hydrolysis of glucose-6-phosphate. Dysregulation of G6PC1 gene…

The molecular basis for the role of apolipoprotein A-II in cholesterol and triglyceride metabolism

Lead Institution

Pacific Northwest National Laboratory

Principal Investigator

John Melchior

Apolipoprotein (apo)A-II is an abundant human plasma protein primarily in high-density lipoproteins (HDL) but also in very low density lipoproteins (VLDL) and chylomicrons. Despite a large literature…

Structure and mechanism of neurotransmitter-gated ion channels

Lead Institution

Oregon Health & Science University

Principal Investigator

Eric Gouaux

The objectives of this research are to elucidate the structures of mammalian neurotransmitter receptors by single particle cryo-EM in multiple distinct conformational states in which the receptors…

Development of in vitro glycosylation toolkit to study eukaryotic glycoproteins

Lead Institution

Environmental Molecular Sciences Laboratory

Principal Investigator

Irina El Khoury

When working with glycoproteins from native sources, biochemical analysis is often hampered by sample heterogeneity and glycan-postprocessing structural diversity. It is therefore desirable to create…

Structure of the first purified manganese oxidase Mnx

Lead Institution

University of Washington

Principal Investigator

Bradley Tebo

This project aims to obtain high-resolution atomic structure of the first purified bacterial manganese-oxidizing complex, Mnx. This complex, containing the novel multicopper oxidase MnxG enzyme, has…

Toward the visualization of eukaryotic transcription machineries by cryo-EM

Lead Institution

Northwestern University

Principal Investigator

Yuan He

Eukaryotic genomes are modulated by different types of chromatin remodeling complexes and transcribed by multiple RNA polymerases. Of the three polymerases, Pol I-III, that produce RNA required for…

Validation and functional characterization of transcription factors in wheat using cell-free protein
expression and high-throughput sequencing technologies

Lead Institution

Environmental Molecular Sciences Laboratory

Principal Investigator

Irina El Khoury

This study aims to validate and functionally characterize a family of transcription factors to understand the differences in their deoxyribonucleic acid binding preferences and their potential impact…

The structure of pseudoenzyme PDX1.2 and its complex with active enzyme PDX1.3

Lead Institution

Environmental Molecular Sciences Laboratory

Principal Investigator

James Evans

Aim - Determine the high-resolution structure of the protein PDX1.2 alone and in complex with PDX1.3. PDX1.2 is an important pseudo-enzyme with regulatory roles in vitamin B6 biosynthesis. It…

Interactions of Adeno-associated virus (AAV) with its Cellular Receptor, RAAV

Lead Institution

University of Missouri - Columbia

Principal Investigator

Michael Chapman

AAV is a leading vector for gene therapy, and, through genomic screening, we recently identified the cellular receptor, AAVR. Biochemistry, and early cryo-EM indicate that the different serotype…

CryoEM structures of pancreatic KATP channels

Lead Institution

Oregon Health & Science University

Principal Investigator

Show-Ling Shyng

The ATP-sensitive potassium (KATP) channel formed by four Kir6.2 and four SUR1 subunits regulate insulin secretion in ?-cells by coupling glucose metabolism with membrane excitability. Mutations in…

Determination of inner hair cell stereocilia widening mechanism

Lead Institution

Oregon Health & Science University

Principal Investigator

Peter Barr-Gillespie

Hair cells are the sensory cells of the inner ear, and use the mechanically sensitive hair bundle to detect sound and head movements. Bundles are composed of a hundred or so stereocilia, each of…

Structure, function and aggregation of the lens alpha-crystallins

Lead Institution

Portland State University

Principal Investigator

Steve Reichow

We are applying emerging methods in single particle CryoEM to advance our understanding the molecular mechanisms leading to cataract formation (the leading cause of blindness in the world). The focus…

Structural Analysis of human retinal ABCA4 using single particle cryo-electron microscopy

Lead Institution

University of British Columbia

Principal Investigator

Robert Molday

Stargardt disease (STGD1) is an autosomal recessive, early-onset macular dystrophy associated with reduced visual acuity and a progressive loss in vision. The gene responsible for STGD1 encodes ABCA4…

Structural characterization of BlaR1: A key regulator of beta-lactam resistance in Staphylococcus aureus

Lead Institution

University of British Columbia

Principal Investigator

Natalie Strynadka

Our vision is to develop and use structural biology methods to characterize membrane-associated protein assemblies relevant to antibiotic resistance and bacterial pathogenicity. We are particularly…

Cryo-EM studies of the prothrombinase:prothrombin complex and the protein C anti-coagulant complex

Lead Institution

Saint Louis University

Principal Investigator

Enrico Di Cera

The objective of this study, funded by 2 active NIH grants, is to elucidate the structures of key proteins and their interacting partners of the prothrombinase:prothrombin complex and the protein C…

Cryo-EM studies of the human biogenic amine transporters

Lead Institution

Oregon Health & Science University

Principal Investigator

Eric Gouaux

The aims of the proposed research are to elucidate the first structure of the human dopamine transporter (hDAT) as well as to determine multiple structures of the human serotonin transporter (hSERT)…

Cryo-EM study of alpha-synuclein fibrils with hereditary disease mutation

Lead Institution

University of California, Los Angeles

Principal Investigator

Lin Jiang

With recent advances of cryo-EM technologies, including direct electron detecting cameras, we are now able to probe a broad scope of amyloid fibril structures to a level of molecular detail that has…

Structural study of full-length SARS-Cov-2 Spike proteins by Cryo-EM

Lead Institution

Oregon Health & Science University

Principal Investigator

Liman Zhang

As of February 25th, 2020 there were 80,146 confirmed cases of SARS-Cov-2 infection across the globe. However, no vaccine or drug is available to prevent or treat the infection. Spike protein of SARS…

Projects