Heidi L. Schubert

Heidi L. Schubert, PhD

Languages spoken: English

Academic Information

Departments Primary - Biochemistry

Academic Office Information

heidi@biochem.utah.edu

Research Interests

  • Crystallography, X-Ray
  • Cryogenic Electron Microscopy and Three-Dimensional Reconstruction (cryo-EM)
  • Nucleosome Remodeling and Reorganization
  • HIV

I have investigated the structural basis of protein function and biological interactions for over 25 years with 46 depositions in the protein data bank. These projects span many different biological processes from signal transduction and metabolism to chromatin remodeling. In recent years I have managed the Bacterial Expression (Molecular Biology) Core Facility of the CHEETAH Center (P50 GM082545). In this capacity, I assist with the planning and implementation of recombinant protein expression and purification projects with the goal of characterizing the molecular interactions which enable HIV infection. I have worked with researchers to define and characterize tractable interactions. I have also determined multiple pertinent crystal structures by taking the leading role on all steps from development of expression constructs to interpretation of the refined models. I have expanded my skill set to include Cryo Electron Microscopy working on single particle reconstruction and took the lead on determining the structure of the microtubule-severing protein spastin (Han and Schubert, et al., 2020). I now play a primary role for cryo-EM projects in the Hill Lab, including collecting data and providing guidance and advice for all aspects of sample preparation, data processing, image reconstruction, and structure refinement. I frequently collaborate with other local labs interested in recombinant protein expression combined with structural and mechanistic studies.

Research Statement

My research addresses two fundamental problems in human biology. Physical interactions between HIV and human proteins are critical for infection and can be defined at the atomic level by X-ray crystallography. I also study the mechanism of large chromatin remodeling complexes required for fundamental regulation of a cellular genome. My research involves recombinant protein expression and purification studies with the goal of solving a crystal structure using molecular replacement, anomalous scattering, or isomorphous replacement. As manager of the Macromolecule Crystallography Core Facility I assist with the planning of many projects, advise students/postdocs from many laboratories on best approaches to protein expression and purification, and train users requiring our crystallization robot and imagers.

Education History

Postdoctoral Fellowship University of Utah
 Postdoctoral Fellow
Postdoctoral Fellowship University of York
 Postdoctoral Fellow
Doctoral Training University of Michigan
 PhD
Undergraduate Miami University
 BS

Selected Publications

Journal Article

  1. Zheng Y, Schubert HL, Singh PK, Martins LJ, Engelman AN, DOrso I, Hill CP, Planelles V (2021). Cleavage and Polyadenylation Specificity Factor 6 Is Required for Efficient HIV-1 Latency Reversal. mBio, 12(3), e0109821.
  2. Sarabia I, Novis CL, Macedo AB, Takata H, Nell R, Kakazu JC, Furler RL, Shakya B, Schubert HL, Hill CP, DePaula-Silva AB, Spivak AM, Trautmann L, Planelles V, Bosque A (2021). Activation of the Anti-Oxidative Stress Response Reactivates Latent HIV-1 Through the Mitochondrial Antiviral Signaling Protein Isoform MiniMAVS. Front Immunol, 12, 682182.
  3. Han H, Schubert HL, McCullough J, Monroe N, Purdy MD, Yeager M, Sundquist WI, Hill CP (2019). Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation. J Biol Chem, 295(2), 435-443.
  4. Nielson JR, Fredrickson EK, Waller TC, Rendn OZ, Schubert HL, Lin Z, Hill CP, Rutter J (2017). Sterol Oxidation Mediates Stress-Responsive Vms1 Translocation to Mitochondria. Mol Cell, 68(4), 673-685.e6.
  5. Nielson JR, Fredrickson EK, Waller TC, Rendn OZ, Schubert HL, Lin Z, Hill CP, Rutter J (2017). Sterol Oxidation Mediates Stress-Responsive Vms1 Translocation to Mitochondria. Mol Cell, 68(4), 673-685.
  6. Schubert HL, Wittmeyer J, Kasten MM, Hinata K, Rawling DC, Hroux A, Cairns BR, Hill CP (2013). Structure of an actin-related subcomplex of the SWI/SNF chromatin remodeler. Proc Natl Acad Sci U S A, 110(9), 3345-50.
  7. Bracken CD, Neighbor AM, Lamlenn KK, Thomas GC, Schubert HL, Whitby FG, Howard BR (2011). Crystal structures of a halophilic archaeal malate synthase from Haloferax volcanii and comparisons with isoforms A and G. BMC Struct Biol, 11, 23.
  8. Koirala S, Bui HT, Schubert HL, Eckert DM, Hill CP, Kay MS, Shaw JM (2010). Molecular architecture of a dynamin adaptor: implications for assembly of mitochondrial fission complexes. J Cell Biol, 191(6), 1127-39.
  9. Schubert HL, Zhai Q, Sandrin V, Eckert DM, Garcia-Maya M, Saul L, Sundquist WI, Steiner RA, Hill CP (2010). Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations. Proc Natl Acad Sci U S A, 107(42), 17951-6.
  10. Mabanglo MF, Schubert HL, Chen M, Hill CP, Poulter CD (2010). X-ray structures of isopentenyl phosphate kinase. ACS Chem Biol, 5(5), 517-27.
  11. Zhang J, Wu X, Padovani D, Schubert HL, Gravel RA (2009). Ligand-binding by catalytically inactive mutants of the cblB complementation group defective in human ATP:cob(I)alamin adenosyltransferase. Mol Genet Metab, 98(3), 278-84.
  12. Holliday GL, Thornton JM, Marquet A, Smith AG, Rbeill F, Mendel R, Schubert HL, Lawrence AD, Warren MJ (2007). Evolution of enzymes and pathways for the biosynthesis of cofactors. Nat Prod Rep, 24(5), 972-87.
  13. Frank S, Deery E, Brindley AA, Leech HK, Lawrence A, Heathcote P, Schubert HL, Brocklehurst K, Rigby SE, Warren MJ, Pickersgill RW (2007). Elucidation of substrate specificity in the cobalamin (vitamin B12) biosynthetic methyltransferases. Structure and function of the C20 methyltransferase (CbiL) from Methanothermobacter thermautotrophicus. J Biol Chem, 282(33), 23957-69.