Positions

Overview

  • Our goal is using cryo-EM to understand and design large assemblies.

    Large protein assemblies in nature are universal and essential. They represent a unique gold mine to identify functional modules that display seemingly simple molecular architectures analogous to each LEGO piece; when assembled, they form remarkably complex structures. Our research program aims to discover and understand the biochemical principle behind those nature’s LEGO, especially microbial appendages involved in pathologies, microbial ecology, and bioenergetics. Ultimately, the Wang lab seeks to apply these biochemical rules to design peptide/protein modules that can assemble into functional nanotubes for biomedical applications. Three research directions are available:

    How do microbes make long-range electron transfer happen?
    In anoxic environments, from aquatic sediments to the human gut, respiring bacteria naturally transfer electrons on the micron-scale beyond their outer membranes to distant and insoluble terminal electron acceptors. We generated the first atomic structure of Geobacter conductive nanowires (Cell, 2019), and the atomic structure now reveals the unexpected identity of the conductive nanowires to be polymerized hexa-heme c-type cytochromes. Hemes within OmcS fibers are arranged in a continuous axial chain inside the fiber core, with inter-heme distances from ~3.5-6.0 Å. This is an exciting and new area of research, and our lab uses cryo-EM to understand and design heme-based microbial conductive nanowires.

    Nanotube design in new frontiers in anti-tumor nanomedicine
    The rationale and motivation for this project are: we have observed many fascinating functions from viruses and microbial pili. However, they cannot self-assemble and a large assembling machine is typically needed to put them together, which greatly limits their engineering potential and biomedical applications. While protein self-assembly is a ubiquitous phenomenon in nature, we aim to combine prior knowledge and design self-assembled nanotubes with different structural modules for new biomedical purposes, especially for cancer therapy.

    De novo protein identification from cryo-EM maps
    The recent revolution in cryo-electron microscopy has made it possible to determine macromolecular structures directly from cell extracts. However, identifying the correct protein from the cryo-EM map is still challenging and often needs additional sequence information from other techniques, such as tandem mass spectrometry and/or bioinformatics. AlphaFold made this process easier. But eyeballing an EM map against 2,000 AlphaFold predictions is still painful, like decrypting hieroglyphs. One of our long-term goals is to develop server-based approaches to directly identify proteins from EM maps, without the need for additional information.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2022 Convergent evolution in the supercoiling of prokaryotic flagellar filamentsCell.  185:3487-3500.e14. 2022
    2022 Cryo-EM of Helical PolymersChemical Reviews.  122:14055-14065. 2022
    2022 Structure of Geobacter OmcZ filaments suggests extracellular cytochrome polymers evolved independently multiple timeseLife.  11. 2022
    2022 DeepTracer-ID: De novo protein identification from cryo-EM mapsBiophysical Journal.  121:2840-2848. 2022
    2022 Cryo-EM structure of an extracellular Geobacter OmcE cytochrome filament reveals tetrahaem packingNature Microbiology.  7:1291-1300. 2022
    2022 Enzyme Responsive Rigid-Rod Aromatics Target "Undruggable" Phosphatases to Kill Cancer Cells in a Mimetic Bone MicroenvironmentJournal of the American Chemical Society.  144:13055-13059. 2022
    2022 Mating pair stabilization mediates bacterial conjugation species specificityNature Microbiology.  7:1016-1027. 2022
    2022 Spindle-shaped archaeal viruses evolved from rod-shaped ancestors to package a larger genomeCell.  185:1297-1307.e11. 2022
    2022 Atomic structure of Lanreotide nanotubes revealed by cryo-EM 2022
    2021 Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterialsNature Communications.  12. 2021
    2021 Deterministic chaos in the self-assembly of β sheet nanotubes from an amphipathic oligopeptide 2021
    2021 Adnaviria: A new realm for archaeal filamentous viruses with linear A-form double-stranded DNA genomesJournal of Virology.  95. 2021
    2021 Cryo-EM is a powerful tool, but helical applications can have pitfallsSoft Matter.  17:3291-3293. 2021
    2021 Structure of a filamentous virus uncovers familial ties within the archaeal virosphereVirus Evolution.  6. 2021
    2020 The structures of two archaeal type IV pili illuminate evolutionary relationshipsNature Communications.  11. 2020
    2020 Structures of filamentous viruses infecting hyperthermophilic archaea explain DNA stabilization in extreme environments 2020
    2020 Artificial Intracellular FilamentsCell Reports Physical Science.  1. 2020
    2020 Structural Determination of a Filamentous Chaperone to Fabricate Electronically Conductive Metalloprotein NanowiresACS Nano.  14:6559-6569. 2020
    2020 The structure of helical lipoprotein lipase reveals an unexpected twist in lipase storage 2020
    2019 A packing for A-form DNA in an icosahedral virus 2019
    2019 An extensively glycosylated archaeal pilus survives extreme conditionsNature Microbiology.  4:1401-1410. 2019
    2019 Structure of Microbial Nanowires Reveals Stacked Hemes that Transport Electrons over MicrometersCell.  177:361-369.e10. 2019
    2019 Ambidextrous helical nanotubes from self-assembly of designed helical hairpin motifs 2019
    2018 Structural conservation in a membrane-enveloped filamentous virus infecting a hyperthermophilic acidophileNature Communications.  9. 2018
    2018 Functional role of the type 1 pilus rod structure in mediating host-pathogen interactionseLife.  7. 2018
    2017 A structural model of flagellar filament switching across multiple bacterial speciesNature Communications.  8. 2017
    2017 Structural basis for high-affinity actin binding revealed by a β-III-spectrin SCA5 missense mutationNature Communications.  8. 2017
    2017 Cryoelectron Microscopy Reconstructions of the Pseudomonas aeruginosa and Neisseria gonorrhoeae Type IV Pili at Sub-nanometer ResolutionFolding & design.  25:1423-1435.e4. 2017
    2017 Refined Cryo-EM Structure of the T4 Tail Tube: Exploring the Lowest Dose LimitFolding & design.  25:1436-1441.e2. 2017
    2016 Reader domain specificity and lysine demethylase-4 family functionNature Communications.  7. 2016
    2016 Functional AdoMet Isosteres Resistant to Classical AdoMet Degradation PathwaysACS Chemical Biology.  11:2484-2491. 2016
    2016 Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphateStructural Dynamics.  3. 2016
    2015 Structural Basis for the Stereochemical Control of Amine Installation in Nucleotide Sugar AminotransferasesACS Chemical Biology.  10:2048-2056. 2015
    2015 Structural characterization of AtmS13, a putative sugar aminotransferase involved in indolocarbazole AT2433 aminopentose biosynthesis 2015
    2015 Structure of a cupin protein Plu4264 from Photorhabdus luminescens subsp. laumondii TTO1 at 1.35 Å resolution 2015
    2014 Structure-guided functional characterization of enediyne self-sacrifice resistance proteins, CalU16 and CalU19ACS Chemical Biology.  9:2347-2358. 2014
    2014 Understanding molecular recognition of promiscuity of thermophilic methionine adenosyltransferase sMAT from Sulfolobus solfataricus 2014
    2014 Crystal structure of thermostable p-nitrophenylphosphatase from bacillus stearothermophilus (Bs-TpNPPase) 2014
    2013 Crystal structure of SsfS6, the putative C-glycosyltransferase involved in SF2575 biosynthesis 2013
    2012 Crystal structure of the Tum1 protein from the yeast saccharomyces cerevisiae 2012
    2011 Crystallization and preliminary X-ray analysis of the yeast tRNA-thiouridine modification protein 1 (Tum1p)Acta Crystallographica Section F: Structural Biology Communications.  67:953-955. 2011
    2011 The dual role of ubiquitin-like protein Urm1 as a protein modifier and sulfur carrier 2011

    Research Overview

  • Read more on the lab webpage: https://jerryuab.org/
  • Education And Training

  • Doctor of Philosophy in Biochemistry, Biophysics and Molecular Biology, Rice University 2016
  • Full Name

  • Fengbin Wang