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Jochen Zimmer

Jochen Zimmer

HHMI Investigator and Professor, Molecular Physiology and Biological Physics

Primary Location
380 Snyder Research Bldg.
Fontaine Research Park, 480 Ray C. Hunt Dr.
Primary Phone Number
434.243.6506
Email
[email protected]
Website
https://jochenzimmer.faculty.virginia.edu/

Bio & Overview

Under certain conditions, all essential biopolymers, such as polypeptides, nucleic acids and polysaccharides, have to cross at least one membrane to reach their final destinations. Examples include the secretion of antibodies, export of RNA from the nucleus and the deposition of polysaccharides in the extracellular matrix. While our knowledge has expended significantly on the translocation and membrane integration of polypeptides, very little is known about how one of the most hydrophilic polymers, the polysaccharide, can cross the hydrophobic barrier surrounding every cell. Polysaccharides come in many forms and serve a multitude of different functions. For example, starch and glycogen are means of energy storage, cellulose and chitin confer structural stability to the cell, and hyaluronan modulates cell differentiation, proliferation and migration in vertebrates. To serve their ultimate purpose, many of these polysaccharides, which can be several microns in length, have to be transported across lipid bilayers. In many cases, membrane embedded processive polysaccharide synthases connect intracellular building blocks (activated sugars) and translocate the growing polysaccharide chain across the membrane. This process requires (1) the recognition and binding of the activated sugars by intracellular catalytic domains, (2) a glycosyltransferase activity to covalently link the building blocks, (3) the formation of a transmembrane channel, and (4) the translocation of the growing polysaccharide chain through the channel. Combined, this process couples the biosynthesis of extremely long linear polysaccharides with their membrane translocation, catalyzed by a single enzyme. Studying the translocation of polysaccharides across biological membranes necessitates a broad spectrum of techniques. Initially, target proteins will be cloned, expressed, and purified. With high quality material in hand, biophysical and biochemical studies follow. A major aim of the laboratory is the structural characterization of glycosyltransferases involved in hyaluronan, cellulose and curdlan biosynthesis. Simultaneously, we strive to establish in vitro polysaccharide translocation assays by reconstituting purified enzymes into proteoliposomes, which are a convenient tool to study membrane transport processes. This will allow us to (1) reproduce the biosynthesis and translocation of the polymer outside the cell, (2) develop assays that identify the path of the polysaccharide through the membrane channel, and (3) identify conditions that will trap translocation intermediates for structural studies. As an interdisciplinary approach, we will also use electron microscopy to study the supra-molecular assemblies some of the glycosyltransferases form in native membranes as well as cell biology techniques to study the surface expression of matrix polysaccharides in a physiological context. Techniques to be applied: Recombinant DNA and molecular biology techniques Heterologous protein expression in bacterial and eukaryotic systems Reconstitution of proteins into lipid vesicles Enzyme activity assays Protein purification (metal affinity-, ion exchange- and gel filtration chromatography) X-ray crystallography https://www.ncbi.nlm.nih.gov/pubmed/?term=Zimmer+J+AND+Virginia+%5BAD%5D List of Publications in Pubmed

Academic Information

Department
Molecular Physiology and Biological Physics
Academic Title
Assistant Professor

Primary Education

  • Diploma, Biophysics, ETH Zurich, 2000
  • PhD, Biophysics, University of Oxford, 2004
  • Postdoc, Biophysics, Harvard Medical School, 2009

Other Appointments

  • Assistant Professor, SCBB
  • Assistant Professor, MOMD

Other Affiliations

  • Member, Chemical and Structural Biology Program
  • Assistant Professor, BIMS

Research Interests

Transport of biopolymers across biological membranes with a particular interest in polysaccharide and protein translocation.

Research Disciplines

  • Biochemistry
  • Biophysics
  • Biophysics & Structural Biology
  • Cancer Biology
  • Infectious Diseases/Biodefense
  • Molecular Biology
  • Physiology
  • Structural Biology

Research Opportunities

  • Biochemistry
  • Biophysics & Structural Biology
  • Cancer Biology
  • Chemistry and Physics of Living Systems
  • Infectious Diseases
  • Molecular Biology

PhD Programs

  • Biophysics
  • Physiology

Selected Publications

2024

Lampugnani, E. R., Ford, K., Ho, Y. Y., van de Meene, A., Lahnstein, J., Tan, H. -T., . . . Roberts, E. M. (2024). Glycosyl transferase GT2 genes mediate the biosynthesis of an unusual (1,3;1,4)-β-glucan exopolysaccharide in the bacterium Sarcina ventriculi. MOLECULAR MICROBIOLOGY, 121(6), 1245-1261. doi:10.1111/mmi.15276

Kuklewicz, J., & Zimmer, J. (2024). Molecular insights into capsular polysaccharide secretion. NATURE, 628(8009). doi:10.1038/s41586-024-07248-9

2023

DeAngelis, P. L., & Zimmer, J. (2023). Hyaluronan synthases; mechanisms, myths, & mysteries of three types of unique bifunctional glycosyltransferases. GLYCOBIOLOGY, 33(12), 1117-1127. doi:10.1093/glycob/cwad075

Hrmova, M., Zimmer, J., Bulone, V., & Fincher, G. B. (2023). Enzymes in 3D: Synthesis, remodelling, and hydrolysis of cell wall (1,3;1,4)-β-glucans. PLANT PHYSIOLOGY, 194(1), 33-50. doi:10.1093/plphys/kiad415

Verma, P., Kwansa, A. L., Ho, R., Yingling, Y. G., & Zimmer, J. (2023). Insights into substrate coordination and glycosyl transfer of poplar cellulose synthase-8. STRUCTURE, 31(10), 1166-+. doi:10.1016/j.str.2023.07.010

Stephens, Z., Wilson, L. F. L., & Zimmer, J. (2023). Diverse mechanisms of polysaccharide biosynthesis, assembly and secretion across kingdoms. CURRENT OPINION IN STRUCTURAL BIOLOGY, 79. doi:10.1016/j.sbi.2023.102564

2022

Purushotham, P., Ho, R., Yu, L., Fincher, G. B., Bulone, V., & Zimmer, J. (2022). Mechanism of mixed-linkage glucan biosynthesis by barley cellulose synthase-like CslF6 (1,3;1,4)-β-glucan synthase. SCIENCE ADVANCES, 8(45). doi:10.1126/sciadv.add1596

Spellmon, N., Muszynski, A., Gorniak, I., Vlach, J., Hahn, D., Azadi, P., & Zimmer, J. (2022). Molecular basis for polysaccharide recognition and modulated ATP hydrolysis by the O antigen ABC transporter. NATURE COMMUNICATIONS, 13(1). doi:10.1038/s41467-022-32597-2

Maloney, F. P., Kuklewicz, J., Corey, R. A., Bi, Y., Ho, R., Mateusiak, L., . . . Zimmer, J. (2022). Structure, substrate recognition and initiation of hyaluronan synthase. NATURE, 604(7904), 195-+. doi:10.1038/s41586-022-04534-2

2021

Xue, J., Purushotham, P., Acheson, J. F., Ho, R., Zimmer, J., McFarlane, C., . . . Samuels, A. L. (2022). Functional characterization of a cellulose synthase, CtCESA1, from the marine red alga Calliarthron tuberculosum (Corallinales). JOURNAL OF EXPERIMENTAL BOTANY, 73(3), 680-695. doi:10.1093/jxb/erab414

Acheson, J. F., Ho, R., Goularte, N. F., Cegelski, L., & Zimmer, J. (2021). Molecular organization of the E. coli cellulose synthase macrocomplex. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 28(3). doi:10.1038/s41594-021-00569-7

2020

Caffalette, C. A., & Zimmer, J. (2021). Cryo-EM structure of the full-length WzmWzt ABC transporter required for lipid-linked O antigen transport. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 118(1). doi:10.1073/pnas.2016144118

Thomas, C., Aller, S. G., Beis, K., Carpenter, E. P., Chang, G., Chen, L., . . . Tampe, R. (2020). Structural and functional diversity calls for a new classification of ABC transporters. FEBS LETTERS, 594(23), 3767-3775. doi:10.1002/1873-3468.13935

Purushotham, P., Ho, R., & Zimmer, J. (2020). Architecture of a catalytically active homotrimeric plant cellulose synthase complex. SCIENCE, 369(6507), 1089-+. doi:10.1126/science.abb2978

Caffalette, C. A., Kuklewicz, J., Spellmon, N., & Zimmer, J. (2020). Biosynthesis and Export of Bacterial Glycolipids. ANNUAL REVIEW OF BIOCHEMISTRY, VOL 89, 89, 741-768. doi:10.1146/annurev-biochem-011520104707

2019

Bi, Y., & Zimmer, J. (2020). Structure and Ligand-Binding Properties of the O Antigen ABC Transporter Carbohydrate-Binding Domain. STRUCTURE, 28(2), 252-+. doi:10.1016/j.str.2019.11.020

Acheson, J. F., Derewenda, Z. S., & Zimmer, J. (2019). Architecture of the Cellulose Synthase Outer Membrane Channel and Its Association with the Periplasmic TPR Domain. STRUCTURE, 27(12), 1855-+. doi:10.1016/j.str.2019.09.008

Caffalette, C. A., Corey, R. A., Sansom, M. S. P., Stansfeld, P. J., & Zimmer, J. (2019). A lipid gating mechanism for the channel-forming O antigen ABC transporter. NATURE COMMUNICATIONS, 10. doi:10.1038/s41467-019-08646-8

Zimmer, J. (2019). Structural features underlying recognition and translocation of extracellular polysaccharides. INTERFACE FOCUS, 9(2). doi:10.1098/rsfs.2018.0060

2018

Bi, Y., Mann, E., Whitfield, C., & Zimmer, J. (2018). Architecture of a channel-forming O-antigen polysaccharide ABC transporter. NATURE, 553(7688), 361-+. doi:10.1038/nature25190

2017

Blackburn, M. R., Hubbard, C., Kiessling, V., Bi, Y., Kloss, B., Tamm, L. K., & Zimmer, J. (2018). Distinct reaction mechanisms for hyaluronan biosynthesis in different kingdoms of life. GLYCOBIOLOGY, 28(2), 108-121. doi:10.1093/glycob/cwx096

Cho, S. H., Purushotham, P., Fang, C., Maranas, C., Diaz-Moreno, S. M., Bulone, V., . . . Nixon, B. T. (2017). Synthesis and Self-Assembly of Cellulose Microfibrils from Reconstituted Cellulose Synthase. PLANT PHYSIOLOGY, 175(1), 146-156. doi:10.1104/pp.17.00619

Morgan, J. L. W., Acheson, J. F., & Zimmer, J. (2017). Structure of a Type-1 Secretion System ABC Transporter. STRUCTURE, 25(3), 522-529. doi:10.1016/j.str.2017.01.010

Basu, S., Omadjela, O., Zimmer, J., & Catchmark, J. M. (2017). Impact of plant matrix polysaccharides on cellulose produced by surface-tethered cellulose synthases. CARBOHYDRATE POLYMERS, 162, 93-99. doi:10.1016/j.carbpol.2017.01.005

2016

Purushotham, P., Cho, S. H., Diaz-Moreno, S. M., Kumar, M., Nixon, B. T., Bulone, V., & Zimmer, J. (2016). A single heterologously expressed plant cellulose synthase isoform is sufficient for cellulose microfibril formation in vitro. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(40), 11360-11365. doi:10.1073/pnas.1606210113

Morgan, J. L. W., McNamara, J. T., Fischer, M., Rich, J., Chen, H. -M., Withers, S. G., & Zimmer, J. (2016). Observing cellulose biosynthesis and membrane translocation in crystallo. NATURE, 531(7594), 329-+. doi:10.1038/nature16966

Knott, B. C., Crowley, M. F., Himmel, M. E., Zimmer, J., & Beckham, G. T. (2016). Simulations of cellulose translocation in the bacterial cellulose synthase suggest a regulatory mechanism for the dimeric structure of cellulose. CHEMICAL SCIENCE, 7(5), 3108-3116. doi:10.1039/c5sc04558d

Basu, S., Omadjela, O., Gaddes, D., Tadigadapa, S., Zimmer, J., & Catchmark, J. M. (2016). Cellulose Microfibril Formation by Surface-Tethered Cellulose Synthase Enzymes. ACS NANO, 10(2), 1896-1907. doi:10.1021/acsnano.5b05648

2015

Bi, Y., Hubbard, C., Purushotham, P., & Zimmer, J. (2015). Insights into the structure and function of membrane-integrated processive glycosyltransferases. CURRENT OPINION IN STRUCTURAL BIOLOGY, 34, 78-86. doi:10.1016/j.sbi.2015.07.008

Schwerdt, J. G., MacKenzie, K., Wright, F., Oehme, D., Wagner, J. M., Harvey, A. J., . . . Fincher, G. B. (2015). Evolutionary Dynamics of the Cellulose Synthase Gene Superfamily in Grasses. PLANT PHYSIOLOGY, 168(3), 968-983. doi:10.1104/pp.15.00140

Yang, H., Zimmer, J., Yingling, Y. G., & Kubicki, J. D. (2015). How Cellulose Elongates-A QM/MM Study of the Molecular Mechanism of Cellulose Polymerization in Bacterial CESA. JOURNAL OF PHYSICAL CHEMISTRY B, 119(22), 6525-6535. doi:10.1021/acs.jpcb.5b01433

McNamara, J. T., Morgan, J. L. W., & Zimmer, J. (2015). A Molecular Description of Cellulose Biosynthesis. ANNUAL REVIEW OF BIOCHEMISTRY, VOL 84, 84, 895-921. doi:10.1146/annurev-biochem-060614-033930

Poulos, S., Morgan, J. L. W., Zimmer, J., & Faham, S. (2015). Bicelles Coming of Age: An Empirical Approach to Bicelle Crystallization. MEMBRANE PROTEINS - ENGINEERING, PURIFICATION AND CRYSTALLIZATION, 557, 393-416. doi:10.1016/bs.mie.2014.12.024

2014

Morgan, J. L. W., McNamara, J. T., & Zimmer, J. (2014). Mechanism of activation of bacterial cellulose synthase by cyclic di-GMP. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 21(5), 489-+. doi:10.1038/nsmb.2803

2013

Slabaugh, E., Davis, J. K., Haigler, C. H., Yingling, Y. G., & Zimmer, J. (2014). Cellulose synthases: new insights from crystallography and modeling. TRENDS IN PLANT SCIENCE, 19(2), 99-106. doi:10.1016/j.tplants.2013.09.009

Omadjela, O., Narahari, A., Strumillo, J., Melida, H., Mazur, O., Bulone, V., & Zimmer, J. (2013). BcsA and BcsB form the catalytically active core of bacterial cellulose synthase sufficient for in vitro cellulose synthesis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(44), 17856-17861. doi:10.1073/pnas.1314063110

Sethaphong, L., Haigler, C. H., Kubicki, J. D., Zimmer, J., Bonetta, D., DeBolt, S., & Yingling, Y. G. (2013). Tertiary model of a plant cellulose synthase. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(18), 7512-7517. doi:10.1073/pnas.1301027110

Zimmer, J. (2013). Synthesis and Membrane Translocation of Cellulose. GLYCOBIOLOGY, 23(11), 1333. Retrieved from https://www.webofscience.com/

2012

Morgan, J. L. W., Strumillo, J., & Zimmer, J. (2013). Crystallographic snapshot of cellulose synthesis and membrane translocation. NATURE, 493(7431), 181-U192. doi:10.1038/nature11744

Hubbard, C., McNamara, J. T., Azumaya, C., Patel, M. S., & Zimmer, J. (2012). The Hyaluronan Synthase Catalyzes the Synthesis and Membrane Translocation of Hyaluronan. JOURNAL OF MOLECULAR BIOLOGY, 418(1-2), 21-31. doi:10.1016/j.jmb.2012.01.053

Zimmer, J. (2012). Hyaluronan synthases catalyze the synthesis and membrane translocation of hyaluronan. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 243. Retrieved from https://www.webofscience.com/

2011

Mazur, O., & Zimmer, J. (2011). Apo- and Cellopentaose-bound Structures of the Bacterial Cellulose Synthase Subunit BcsZ. JOURNAL OF BIOLOGICAL CHEMISTRY, 286(20), 17601-17606. doi:10.1074/jbc.M111.227660

2010

Zhou, Y., Meraner, P., Kwon, H. T., Machnes, D., Oh-hora, M., Zimmer, J., . . . Hogan, P. G. (2010). Minimal Requirement for Store-Operated Calcium Entry: STIM1 Gates ORAI1 Channels in Vitro. BIOPHYSICAL JOURNAL, 98(3), 97A. doi:10.1016/j.bpj.2009.12.546