Harry Scott

Protein complexes involved in building and maintaining the bacterial cell envelope

Lead Institution

New York University School of Medicine

Principal Investigator

Gira Bhabha

In double-membraned bacteria, the outer membrane forms a barrier between the cell and the outside world, and acts as the first line of defense against the environment. The outer membrane in double…

Structure and function of the Gbeta5-CCT complex

Lead Institution

University of Utah

Principal Investigator

Peter Shen

The cytosolic chaperonin CCT is a large, 1 MDa protein folding machine that plays a central role in maintaining the cellular proteome. CCT contributes to proteome homeostasis by assisting in the…

Structural characterization of essential enzymes in bacterial wall teichoic acid biogenesis

Lead Institution

University of British Columbia

Principal Investigator

Natalie Strynadka

Wall teichoic acid (WTA) is a Gram-positive bacterial cell wall polymer with roles in host cell adherence and coordination of essential physiological processes including cell division and…

Structural studies of a bacterial dicarboxylate transporter

Lead Institution

New York University School of Medicine

Principal Investigator

Da-Neng Wang

Human cells import citrate as an energy source through the sodium driven citrate transporter NaCT in the plasma membrane. A bacterial homolog of NaCT is the Vibro succinate transporter VcINDY. We aim…

Medical Defenses Against Emerging Infectious Disease

Lead Institution

La Jolla Institute for Immunology

Principal Investigator

Erica Saphire

Hemorrhagic fever viruses like Ebola, Marburg, and Lassa cause up to 90% lethality. To study these re-emerging threats to human health and develop the needed vaccines and antivirals, our laboratory…

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

Lead Institution

University of Wisconsin, Madison

Principal Investigator

Paul Ahlquist

SARS-CoV-2, Zika, Dengue, and many other dangerous viruses belong to the positive-strand RNA((+)RNA) viruses. Our group first used cryo-electron tomography (cryo-ET) to reveal the organization of…

Structural mechanisms of Acinetobacter baumannii multidrug efflux pumps

Lead Institution

Case Western Reserve University

Principal Investigator

Chih-Chia Su

Acinetobacter baumannii has emerged as one of the most problematic and highly antibiotic-resistant pathogens. A. baumannii infections in military personnel injured in Iraq and Afghanistan were so…

Targeting the PP2A phosphatome with structure-based drug design and a selective heterotrimeric binding pocket.

Lead Institution

Case Western Reserve University

Principal Investigator

Derek Taylor

A major serine/threonine phosphatase, Protein Phosphatase 2A (PP2A), is responsible for the majority of cellular phosphatase activity under physiologic conditions and is dysregulated in an array of…

Single-particle cryo-EM structural analysis of Q-dependent transcription antitermination

Lead Institution

Rutgers University

Principal Investigator

Richard Ebright

The transcription antitermination factor Q, produced by lambdoid bacteriophages, is a textbook example of a regulator of gene expression that functions at the level of transcription termination. Q…

Cryo-EM studies of human TRPM2 channel

Lead Institution

Van Andel Research Institute

Principal Investigator

Juan Du

TRPM2, a Ca2+-permeable, nonselective cation channel belonging to the melastatin subfamily of the TRP superfamily, acts as a major “warmth sensor” in the hypothalamus to regulate core body…

Decommissioning of protein phosphatase 2A holoenzymes

Lead Institution

University of Wisconsin, Madison

Principal Investigator

Yongna Xing

Protein phosphatase 2A (PP2A) is a major tumor suppressor and plays a critical role in many essential cellular processes via formation of diverse heterotrimeric holoenzymes. Each holoenzyme contains…

PNCC Standard Access - Structural insights into bacterial divisome "Fts" proteins

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 aim to illuminate…

Visualizing the molecular mechanisms of synaptic vesicle transporters

Lead Institution

University of Pittsburgh

Principal Investigator

Jonathan Coleman

Approximately 1% of the population experiences seizures, making epilepsy one of the most common neurological disorders. The impact on the livelihood of an individual is, in many ways unfathomable and…

Structural Investigations of the PH Sensing and Drug Inhibition Mechanisms of Proton Activation
Chloride (PAC) Channel

Lead Institution

Van Andel Research Institute

Principal Investigator

Juan Du

Proton-activation chloride channel (PAC) is a ubiquitously expressed ion channel that is responsible for the acid-induced chloride current (I Cl,H ) present in mammalian cells. The molecular identity…

Determining Structures of the APOBEC3-HIV-1 Vif-E3 Ligase Complexes

Lead Institution

University of Minnesota

Principal Investigator

Nadine Shaban

The APOBEC3 family of cytosine deaminases are antiviral factors that can restrict the replication of HIV-1. The virus eliminates this threat by encoding a small protein called Vif that hijacks the…

Structural Investigations of Human TRPM4

Lead Institution

Van Andel Research Institute

Principal Investigator

Wei Lu

The aim of this research is to complete the gating cycle of human TRPM4 by solving the structures at multiple functional states at high-resolution. The recently published TRPM4 structures by our lab…

Cryo-EM studies of nicotinic acetylcholine receptors

Lead Institution

University of Texas Southwestern Medical Center

Principal Investigator

Ryan Hibbs

Nicotinic acetylcholine receptors mediate fast chemical neurotransmission throughout the central and peripheral nervous systems. Nicotinic receptors in the brain are the first point of action…

Structural determination of CALHM channels

Lead Institution

Van Andel Research Institute

Principal Investigator

Wei Lu

The calcium homeostasis modulators (CALHMs) are one of the key ATP release channel families, consisting of three members, CALHM1, 2 and 3. They are voltage-dependent, extracellular,…

Structural mechanisms of the polycystic kidney disease proteins

Lead Institution

University of Utah

Principal Investigator

Erhu Cao

Polycystin-1 and polycystin-2 (also known as PKD1 and PKD2) are fundamental for normal development and functioning of the renal and cardiovascular systems. Mutations in either PKD1 or PKD2 genes…

Structural biology of synaptic and extrasynaptic GABAA receptors

Lead Institution

University of Texas Southwestern Medical Center

Principal Investigator

Ryan Hibbs

GABAA receptors are pentameric ligand-gated ion channels and mediate the majority of fast inhibitory signaling in the brain. Here we propose to characterize the structural pharmacology of receptors…

Collaborative Access Team: Pacific Northwest Cryo-EM Center (PNCC)

Lead Institution

Environmental Molecular Sciences Laboratory

Principal Investigator

James Evans

PNNL will create and operate the Pacific Northwest Center for Cryo-EM (PNCC), a state-of-the-art national center for cryo-electron microscopy (Cryo-EM) that will rapidly and efficiently collect and…

Cryo-EM studies of an ABC transporter complex (NosDFYL)

Lead Institution

Van Andel Research Institute

Principal Investigator

Juan Du

The biological nitrogen cycle describe the enzymatic interconversion of the different chemical forms of nitrogen. In nature, microorganisms make use a huge variety of enzymes in order to perform…

Structure determination of transthyretin amyloid fibrils extracted from amyloidosis patients

Lead Institution

University of Texas Southwestern Medical Center

Principal Investigator

Lorena Saelices

Here, we aim to use cryo-electron microscopy to determine the structures of full-length transthyretin fibrils extracted from autopsied or explanted hearts from ATTR patients carrying either a wild…

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 basis of regulation of PKD2 by steroids

Lead Institution

University of Utah

Principal Investigator

Erhu Cao

Polycystic kidney disease 1 (PKD1) and PKD2 are fundamental for normal development and functioning of the renal and cardiovascular systems and, when rendered defective by genetic mutations, cause a…

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…

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…

CryoEM Studies of KdpFABC

Lead Institution

New York University School of Medicine

Principal Investigator

David Stokes

Our project addresses the molecular mechanism of an unusual K+ pump called KdpFABC. In K+ deficient conditions, bacteria induce expression of this pump in order to maintain osmotic conditions…

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 of the RPE65-CCT folding intermediate

Lead Institution

University of Utah

Principal Investigator

Peter Shen

The retinal pigment epithelium 65 kDa protein (RPE65) plays an essential role in human vision by catalyzing the conversion of all-trans retinol esters to 11-cis retinol. This reaction is a key step…

Broad-spectrum inhibitors of ebolavirus entry

Lead Institution

La Jolla Institute for Immunology

Principal Investigator

Erica Saphire

There are six known viruses in the ebolavirus genus, at least three of which are known to cause severe hemorrhagic fever in humans. All ebolaviruses display one surface protein, a glycoprotein termed…

PNCC General Access - Structure-based antibiotic discovery on the bacterial membrane – Penicillin-binding proteins (PBPs)

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 aim to illuminate…

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…

HTLV-1 intasome structural studies

Lead Institution

University of Minnesota

Principal Investigator

Hideki Aihara

Integrase (IN) is an essential viral enzyme that catalyzes the integration of reverse-transcribed retroviral DNA into the host’s chromosome, and human immunodeficiency virus type-1 (HIV-1) IN is the…

Structural studies of the bacterial ribosome: regulation of gene expression, stress tolerance and antibiotic resistance.

Lead Institution

Emory University

Principal Investigator

Christine Dunham

In every living organism, protein synthesis (translation) is catalyzed by a large, dynamic RNA-protein macromolecular complex called the ribosome. We use biochemical, structural and functional…

Cryo-EM Structural Studies of Lentiviral Intasomes

Lead Institution

Salk Institute for Biological Studies

Principal Investigator

Dmitry Lyumkis

A distinct feature of all retroviruses is the ability to integrate their viral DNA (vDNA) into cellular DNA to ensure permanent infection. This process in vivo is catalyzed by the preintegration…

Cryo-EM Analysis of TcdB in Complex with Host Cell Receptors

Lead Institution

Vanderbilt University Medical Center

Principal Investigator

Dana Lacy

Clostridioides difficile infection (CDI) is responsible for the majority of hospital acquired diarrhea cases reported in the United States. The pathology of CDI relies on the activity of three…

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…

Structural characterization of immunogens in complex with antibodies for structure-based vaccine design

Lead Institution

Fred Hutchinson Cancer Research Center

Principal Investigator

Marie Pancera

Although to-date numerous vaccines exist, their mechanism of protection is not always understood. Additionally, there are pathogens such as HIV and Malaria for which vaccines do not exist. Our…

Structural and functional evolution of broadly neutralizing antibodies against HIV-1

Lead Institution

University of Washington

Principal Investigator

Kelly Lee

The HIV-1 Envelope glycoprotein (Env) mediates entry into host immune cells through a series of receptor-driven conformational changes that lead to fusion of the viral and host membranes. As the sole…

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…

Projects