Heidi L. Schubert

Heidi L. Schubert, PhD

Languages spoken: English

Academic Information

Departments Primary - Biochemistry

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

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

Selected Publications

Journal Article

  1. Han H, Schubert HL, McCullough J, Monroe N, Purdy MD, Yeager M, Sundquist WI, Hill C (2020). Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation. The Journal of biological chemistry, 295(2), 435-443. (Read full article)
  2. Frank S, Deery E, Brindley AA, Leech HK, Lawrence A, Heathcote P, Schubert HL, Brocklehurst K, Rigby SE, Warren MJ, Pickersgill R (2007). Elucidation of substrate specificity in the cobalamin (vitamin B12) biosynthetic methyltransferases. Structure and function of the C20 methyltransferase (CbiL) from Methanothermobacter thermautotrophicus. The Journal of biological chemistry, 282(33), 23957-69. (Read full article)
  3. Koirala S, Bui HT, Schubert HL, Eckert DM, Hill CP, Kay MS, Shaw J (2010). Molecular architecture of a dynamin adaptor: implications for assembly of mitochondrial fission complexes. The Journal of cell biology, 191(6), 1127-39. (Read full article)
  4. Holliday GL, Thornton JM, Marquet A, Smith AG, Rébeillé F, Mendel R, Schubert HL, Lawrence AD, Warren M (2007). Evolution of enzymes and pathways for the biosynthesis of cofactors. Natural product reports, 24(5), 972-87. (Read full article)
  5. Schubert HL, Zhai Q, Sandrin V, Eckert DM, Garcia-Maya M, Saul L, Sundquist WI, Steiner RA, Hill C (2010). Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations. Proceedings of the National Academy of Sciences of the United States of America, 107(42), 17951-6. (Read full article)
  6. Schubert HL, Wittmeyer J, Kasten MM, Hinata K, Rawling DC, Héroux A, Cairns BR, Hill C (2013). Structure of an actin-related subcomplex of the SWI/SNF chromatin remodeler. Proceedings of the National Academy of Sciences of the United States of America, 110(9), 3345-50. (Read full article)
  7. Nielson JR, Fredrickson EK, Waller TC, Rendón OZ, Schubert HL, Lin Z, Hill CP, Rutter J (2017). Sterol Oxidation Mediates Stress-Responsive Vms1 Translocation to Mitochondria. Molecular cell, 68(4), 673-685.
  8. Nielson JR, Fredrickson EK, Waller TC, Rendón OZ, Schubert HL, Lin Z, Hill CP, Rutter (2017). Sterol Oxidation Mediates Stress-Responsive Vms1 Translocation to Mitochondria. Molecular cell, 68(4), 673-685.e6. (Read full article)
  9. Zhang J, Wu X, Padovani D, Schubert HL, Gravel R (2009). Ligand-binding by catalytically inactive mutants of the cblB complementation group defective in human ATP:cob(I)alamin adenosyltransferase. Molecular genetics and metabolism, 98(3), 278-84. (Read full article)
  10. Bracken CD, Neighbor AM, Lamlenn KK, Thomas GC, Schubert HL, Whitby FG, Howard B (2011). Crystal structures of a halophilic archaeal malate synthase from Haloferax volcanii and comparisons with isoforms A and G. BMC structural biology, 11, 23. (Read full article)
  11. Mabanglo MF, Schubert HL, Chen M, Hill CP, Poulter C (2010). X-ray structures of isopentenyl phosphate kinase. ACS chemical biology, 5(5), 517-27. (Read full article)
  12. Zheng Y, Schubert HL, Singh PK, Martins LJ, Engelman AN, D'Orso I, Hill CP, Planelles (2021). Cleavage and Polyadenylation Specificity Factor 6 Is Required for Efficient HIV-1 Latency Reversal. mBio, 12(3), e0109821. (Read full article)
  13. 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 (2021). Activation of the Anti-Oxidative Stress Response Reactivates Latent HIV-1 Through the Mitochondrial Antiviral Signaling Protein Isoform MiniMAVS. Frontiers in immunology, 12, 682182. (Read full article)