Wen Jiang

Wen Jiang
Purdue University | Purdue · Department of Biological Sciences

Ph.D.

About

181
Publications
36,780
Reads
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10,633
Citations
Citations since 2017
66 Research Items
5428 Citations
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20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
Introduction
Structural biology of protein complexes involved in cancers, protein amyloids (Tau, prion, A𝛽, TMEM106B, etc.) in neurodegenerative diseases, viruses, and structure-guided drug discovery using cryo-electron microscopy (cryo-EM); Developments of new sample preparation, data collection, and image analysis/3D reconstruction algorithms and software for single particle cryo-EM, correlative light and electron microscopy (CLEM), and electron tomography (ET).
Additional affiliations
September 2005 - present
Purdue University
Position
  • Professor
January 2002 - August 2005
Baylor College of Medicine
Position
  • PostDoc Position
Education
August 1996 - December 2001
Baylor College of Medicine
Field of study
  • Cryo-EM
September 1992 - July 1995
Institute of Biophysics, Chinese Academy of Sciences
Field of study
  • Biophysics
September 1988 - July 1992
Peking University
Field of study
  • Physics

Publications

Publications (181)
Article
Full-text available
The critical viral components for packaging DNA, recognizing and binding to host cells, and injecting the condensed DNA into the host are organized at a single vertex of many icosahedral viruses. These component structures do not share icosahedral symmetry and cannot be resolved using a conventional icosahedral averaging method. Here we report the...
Article
The affinity cryoelectron microscopy (cryo-EM) approach has been explored in recent years to simplify and/or improve the sample preparation for cryo-EM, which can bring previously challenging specimens such as those of low abundance and/or unpurified ones within reach of the cryo-EM technique. Despite the demonstrated successes for solving structur...
Article
Cryo-Electron Tomography (cryo-ET) has become an essential technique in revealing cellular and macromolecular assembly structures in their native states. However, due to radiation damage and the limited tilt range, cryo-ET suffers from low contrast and missing wedge artifacts, which limits the tomograms to low resolution and hinders further biologi...
Article
Full-text available
In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from the brain of individuals affected by Prion-Protein cerebral amyloid angiopathy (PrP-CAA) with a nonsense mutation in the PRNP gene that leads to early...
Article
Full-text available
Prion protein (PrP) aggregation and formation of PrP amyloid (APrP) are central events in the pathogenesis of prion diseases. In the dominantly inherited prion protein amyloidosis known as Gerstmann–Sträussler–Scheinker (GSS) disease, plaques made of PrP amyloid are present throughout the brain. The c.593t > c mutation in the prion protein gene ( P...
Preprint
Background The Microtubule-Associated Protein Tau (MAPT) is one of the proteins that are central to neurodegenerative diseases. The nature of intracellular tau aggregates is determined by the cell types whether neuronal or glial, the participating tau isoforms, and the structure of the amyloid filament. The transmembrane protein 106B (TMEM106B) has...
Article
Protein arginine methyltransferase 5 (PRMT5) is a master epigenetic regulator and an extensively validated therapeutic target in multiple cancers. Notably, PRMT5 is the only PRMT that requires an obligate cofactor, methylosome protein 50 (MEP50), to function. We developed compound 17, a novel small-molecule PRMT5:MEP50 protein-protein interaction (...
Article
Full-text available
Cryogenic electron microscopy (cryoEM) has emerged as a revolutionary method for solving high-resolution structures and studying the dynamics of macromolecular complexes and viruses in near-native states. However, the availability of the equipment, and the time and cost needed for training, severely limit the opportunities for training. To solve th...
Article
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Biological structures with helical symmetries of distinct twist, rise, and axial symmetry are abundant and span a wide range of organisms and functions. Performing de novo helical indexing remains challenging because of the steep learning curve involved in Fourier space layer lines. The unknown amount of out-of-plane tilt and the existence of multi...
Article
Full-text available
Even with implementation of current influenza vaccines, influenza still claims up to 500,000 lives worldwide annually, indicating a need for a better vaccine strategy. We have developed a technology to generate unique S60-HA1 pseudovirus nanoparticles (PVNPs) that display the receptor-binding HA1 domains of influenza viruses. Each self-assembled S6...
Preprint
Full-text available
Antibiotic resistance poses a growing risk to public health requiring new tools to combat pathogenic bacteria. Contractile injection systems, including bacteriophage tails, pyocins, and bacterial type VI secretion systems, can efficiently penetrate cell envelopes and become potential antibacterial agents. Bacteriophage XM1 is a dsDNA virus belongin...
Article
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In Gram-negative bacteria, the biogenesis of β-barrel outer membrane proteins is mediated by the β-barrel assembly machinery (BAM). The mechanism employed by BAM is complex and so far- incompletely understood. Here, we report the structures of BAM in nanodiscs, prepared using polar lipids and native membranes, where we observe an outward-open state...
Article
Full-text available
Phage G is recognized as having a remarkably large genome and capsid size among isolated, propagated phages. Negative stain electron microscopy of the host–phage G interaction reveals tail sheaths that are contracted towards the distal tip and decoupled from the head–neck region. This is different from the typical myophage tail contraction, where t...
Article
Discovery of small-molecule degraders that activate ubiquitin ligase–mediated ubiquitination and degradation of targeted oncoproteins in cancer cells has been an elusive therapeutic strategy. Here, we report a cancer cell–based drug screen of the NCI drug-like compounds library that enabled identification of small-molecule degraders of the small ub...
Article
Full-text available
VCP/p97 is an evolutionarily conserved AAA+ ATPase important for cellular homeostasis. Previous studies suggest that VCP predominantly exists as a homohexamer. Here, we performed structural and biochemical characterization of VCP dodecamer, an understudied state of VCP. The structure revealed an apo nucleotide status that has rarely been captured,...
Preprint
Full-text available
This is the original version of the manuscript that has now been published (http://dx.doi.org/10.3390/v13102094) after revisions.
Preprint
Recent progress in the development of affinity grids for cryoelectron microscopy (cryo-EM) typically employs genetic engineering of the protein sample such as histidine or Spy tagging, immobilized antibody capture, or nonselective immobilization via electrostatic interactions or Schiff base formation. We report a powerful and flexible method for th...
Article
Full-text available
The role of abnormal brain iron metabolism in neurodegenerative diseases is still insufficiently understood. Here, we investigate the molecular basis of the neurodegenerative disease hereditary ferritinopathy (HF), in which dysregulation of brain iron homeostasis is the primary cause of neurodegeneration. We mutagenized ferritin’s three-fold pores...
Article
Full-text available
Chromatin is spatially organized in a hierarchical manner initiating from single nucleosomes condensing into higher order chromatin structures conferring various mechanical properties and biochemical signals. These higher order chromatin structures regulate genomic function by organization of the heterochromatin and euchromatin landscape. Less is k...
Article
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Molecular dynamics techniques provide numerous strategies for investigating biomolecular energetics, though quantitative analysis is often only accessible for relatively small (frequently monomeric) systems. To address this limit, we use simulations in combination with a simplified energetic model to study complex rearrangements in a large assembly...
Article
Full-text available
Encapsulin is a class of nanocompartments that is unique in bacteria and archaea to confine enzymatic activities and sequester toxic reaction products. Here we present a 2.87 Å resolution cryo-EM structure of Thermotoga maritima encapsulin with heterologous protein complex loaded. It is the first successful case of expressing encapsulin and heterol...
Article
Full-text available
Sub-3 Å Apoferritin Structure Determined with Single Position of Volta Phase Plate and Full Range of Phase Shift - Chen Sun, Kunpeng Li, Thomas Klose, Jose Irimia-Dominguez, Frank Vago, Ruben Vidal, Wen Jiang
Article
MBIR 3D Reconstruction Method Effectively Minimizes Missing Wedge Artifacts and Restores Missing Information in Cryo-electron Tomography - Rui Yan, Singanallur Venkatakrishnan, Jun Liu, Charles Bouman, Wen Jiang
Article
JSPR is a single particle cryo-EM image processing and 3D reconstruction software developed in the Jiang laboratory at Purdue University. It began as a few refinement scripts for symmetric and asymmetric reconstructions of icosahedral viruses, but has grown into a comprehensive suite of tools for building ab initio reconstructions, high resolution...
Article
Phage G has the largest capsid and genome of any known propagated phage. Many aspects of its structure, assembly, and replication have not been elucidated. Herein, we present the dsDNA-packed and empty phage G capsid at 6.1 Å and 9 Å resolution, respectively, using cryo-EM for structure determination and mass spectrometry for protein identification...
Article
Members of the family Reoviridae package several copies of the viral polymerase complex into their capsid to carry out replication and transcription within viral particles. Classical single-particle reconstruction encounters difficulties resolving structures such as the intraparticle polymerase complex because refinement can converge to an incorrec...
Article
Full-text available
The naked DNA inside the nucleus interacts with proteins and RNAs forming higher order chromatin structure to spatially and temporally control transcription in eukaryotic cells. The 30 nm chromatin fiber is one of the most important determinants of the regulation of eukaryotic transcription. However, the transition of chromatin from the 30 nm inact...
Article
Full-text available
Volta Phase Plate (VPP) has become an invaluable tool for cryo-EM structural determination of small protein complexes by increasing image contrast. Currently, the standard protocol of VPP usage periodically changes the VPP position to a fresh spot during data collection. Such a protocol was to target the phase shifts to a relatively narrow range (a...
Article
Full-text available
Coxsackievirus A10 (CV-A10) belongs to the Enterovirus species A and is a causative agent of hand, foot, and mouth disease. Here we present cryo-EM structures of CV-A10 mature virion and native empty particle (NEP) at 2.84 and 3.12 Å, respectively. Our CV-A10 mature virion structure reveals a density corresponding to a lipidic pocket factor of 18 c...
Article
Flaviviruses assemble initially in an immature, noninfectious state and undergo extensive conformational rearrangements to generate mature virus. Previous cryo-electron microscopy (cryo-EM) structural studies of flaviviruses assumed icosahedral symmetry and showed the concentric organization of the external glycoprotein shell, the lipid membrane, a...
Article
Full-text available
Phospholipase C (PLC) enzymes produce second messengers that increase the intracellular Ca2+ concentration and activate protein kinase C (PKC). These enzymes also share a highly conserved arrangement of core domains. However, the contributions of the individual domains to regulation are poorly understood, particularly in isoforms lacking high-resol...
Article
Full-text available
Homotypic interactions of viral capsid proteins are common, driving viral capsid self-formation. By taking advantage of such interactions of norovirus shell (S) domain that naturally builds the interior shells of norovirus capsids, we have developed a technology to produce 60-valent, icosahedral S60 nanoparticles through the E. coli system. This ha...
Article
Full-text available
2.5 Ǻ Resolution Cryo-EM Structure of Human Apo-ferritin Using an Optimized Workflow for Volta Phase Plate - Volume 24 Supplement - Kunpeng Li, Thomas Klose, Chen Sun, Yue Liu, Wen Jiang
Preprint
Full-text available
Cryo-Electron Tomography (cryo-ET) has become an essential technique in revealing cellular and macromolecular assembly structures in their native states. However, due to radiation damage and the limited tilt range, cryo-ET suffers from low contrast and missing wedge artifacts, which limits the tomograms to low resolution and hinders further biologi...
Article
Full-text available
Programmed self-assembly of nucleic acids is a powerful approach for nano-constructions. The assembled nanostructures have been explored for various applications. However, nucleic acid assembly often requires chemical or in vitro enzymatical synthesis of DNA or RNA, which is not a cost-effective production method on a large scale. In addition, the...
Article
Full-text available
First step of gene expression is transcribing the genetic information stored in DNA to RNA by the transcription machinery including RNA polymerase (RNAP). In Escherichia coli, a primary sigma70 factor form the RNAP holoenzyme to express housekeeping genes. The sigma70 contains a large insertion at between the conserved regions 1.2 and 2.1, the sigm...
Preprint
Full-text available
First step of gene expression is transcribing the genetic information stored in DNA to RNA by the transcription machinery including RNA polymerase (RNAP). In Escherichia coli , a primary σ ⁷⁰ factor form the RNAP holoenzyme to express housekeeping genes. The σ ⁷⁰ contains a large insertion at between the conserved regions 1.2 and 2.1, the σ non-con...
Article
Full-text available
Daily alignment of the microscope is a prerequisite to reaching optimal lens conditions for high resolution imaging in cryo-EM. In this study, we have investigated how image astigmatism varies with the imaging conditions (e.g. defocus, magnification). We have found that the large change of defocus/magnification between visual correction of astigmat...
Article
Mature double-stranded DNA bacteriophages have capsids with symmetrical shells that typically resist disruption, as they must to survive in the wild. However, flexibility and associated dynamism assist function. We describe biochemistry-oriented procedures used to find previously obscure flexibility for capsids of the related phages, T3 and T7. The...
Article
Full-text available
Studies on dsDNA bacteriophages have revealed that a DNA packaging complex assembles at a special vertex called the ‘portal vertex’ and consists of a portal, a DNA packaging ATPase and other components. AdV protein IVa2 is presumed to function as a DNA packaging ATPase. However, a protein that functions as a portal is not yet identified in AdVs. To...
Article
Marine bacteriophage TW1 belongs to the Siphoviridae family and infects Pseudoalteromonas phenolica. Mass spectrometry analysis has identified 16 different proteins in the TW1 virion. Functions of most of these proteins have been predicted by bioinformatic methods. A 3.6 Å resolution cryoelectron microscopy map of the icosahedrally averaged TW1 hea...
Article
Full-text available
Coxsackievirus A6 (CVA6) has recently emerged as one of the predominant causative agents of hand, foot, and mouth disease (HFMD). The structure of the CVA6 mature viral particle has not been solved thus far. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 represent a promising CVA6 vaccine candidate. Here, we report the...
Article
During the development of single particle cryo-EM in past five decades, icosahedral viruses have led the resolution progress owing to their large mass and high symmetry. Many technical advances in cryo-EM were first established with viruses. Since reaching ∼4 Å resolution in 2008, it has become a relatively routine task to solve the atomic structur...
Article
Full-text available
Significance The WT bacteriophage T4 head is prolate with icosahedral T=13 ends closing the central cylindrical section. The structure of a T=13 icosahedral head assembly, in which the major capsid protein of T4 phage had a single mutation at a residue in the interface between neighboring subunits, has been determined to 3.3-Å resolution. The struc...
Article
Full-text available
Cucumber necrosis virus (CNV) is a member of the genus Tombusvirus and has a monopartite positive-sense RNA genome. CNV is transmitted in nature via zoospores of the fungus Olpidium bornovanus. As with other members of the Tombusvirus genus, the CNV capsid swells when exposed to alkaline pH and EDTA. We previously demonstrated that a P73G mutation...
Article
Full-text available
Significance Rhinoviruses (RVs) frequently cause respiratory infections in humans. However, there are currently no approved antiviral treatments or vaccines available. Using cryo-electron microscopy (cryo-EM), we have shown that the antigen-binding fragment of a neutralizing antibody, C5, binds to RV-B14 and causes significant structural rearrangem...
Preprint
Daily alignment of the microscope is a prerequisite to reaching optimal illumination lens and imaging lens conditions for high resolution imaging in cryo-EM. In contrast to the dramatic progress in automated image acquisition and post-image processing techniques, less attention has been paid to the improvement of microscope alignment before data co...
Article
Full-text available
Significance The enormous prevalence of tailed double-stranded DNA bacteriophages on this planet is made possible by highly efficient self-assembly of usually hundreds of protein subunits into highly stable capsids. These capsids must stand with an internal pressure as a result of the phage DNA-packaging process. Here we report the complete atomic...
Data
Supplementary Figures and Supplementary Table
Article
Full-text available
Significance Electron cryomicroscopy is a rapidly growing field for macromolecular structure determination. We establish a computational protocol to construct a de novo atomic model from a cryo-EM density map, along with associated metadata that describe coordinate uncertainty and the density at each atom. This model faithfully replicates experimen...
Article
Full-text available
The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimens...
Article
Discrete and symmetric three-dimensional (3D) DNA nanocages have been revoked as excellent candidates for various applications, such as guest component encapsulation and organization (e.g. dye molecules, proteins, inorganic nanoparticles, etc.) to construct new materials and devices. To date, a large variety of DNA nanocages has been synthesized th...
Article
The current Zika virus (ZIKV) epidemic is characterized by severe pathogenicity in both children and adults. Sequence changes in ZIKV since its first isolation are apparent when pre-epidemic strains are compared with those causing the current epidemic. However, the residues that are responsible for ZIKV pathogenicity are largely unknown. Here we re...
Article
Minimization of the astigmatism of the objective lens is a critical daily instrument alignment task essential for high resolution TEM imaging. Fast and sensitive detection of astigmatism is needed to provide real-time feedback and adjust the stigmators to efficiently reduce astigmatism. Currently the method used by many microscopists is to visually...