Honors & Awards

  • Graduate Research Fellowship, National Science Foundation (03/2015-06/2020)

All Publications

  • The structural basis of Rubisco phase separation in the pyrenoid. Nature plants He, S., Chou, H., Matthies, D., Wunder, T., Meyer, M. T., Atkinson, N., Martinez-Sanchez, A., Jeffrey, P. D., Port, S. A., Patena, W., He, G., Chen, V. K., Hughson, F. M., McCormick, A. J., Mueller-Cajar, O., Engel, B. D., Yu, Z., Jonikas, M. C. 2020


    Approximately one-third of global CO2 fixation occurs in a phase-separated algal organelle called the pyrenoid. The existing data suggest that the pyrenoid forms by the phase separation of the CO2-fixing enzyme Rubisco with a linker protein; however, the molecular interactions underlying this phase separation remain unknown. Here we present the structural basis of the interactions between Rubisco and its intrinsically disordered linker protein Essential Pyrenoid Component 1 (EPYC1) in the model alga Chlamydomonas reinhardtii. We find that EPYC1 consists of five evenly spaced Rubisco-binding regions that share sequence similarity. Single-particle cryo-electron microscopy of these regions in complex with Rubisco indicates that each Rubisco holoenzyme has eight binding sites for EPYC1, one on each Rubisco small subunit. Interface mutations disrupt binding, phase separation and pyrenoid formation. Cryo-electron tomography supports a model in which EPYC1 and Rubisco form a codependent multivalent network of specific low-affinity bonds, giving the matrix liquid-like properties. Our results advance the structural and functional understanding of the phase separation underlying the pyrenoid, an organelle that plays a fundamental role in the global carbon cycle.

    View details for DOI 10.1038/s41477-020-00811-y

    View details for PubMedID 33230314

  • SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress MOLECULAR CELL Szoradi, T., Schaeff, K., Garcia-Rivera, E. M., Itzhak, D. N., Schmidt, R. M., Bircham, P. W., Leiss, K., Diaz-Miyar, J., Chen, V. K., Muzzey, D., Borner, G. H., Schuck, S. 2018; 70 (6): 1025-+


    When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activities during stress. Here, we uncover a regulatory cascade in budding yeast that consists of the hydrophilin protein Roq1/Yjl144w, the HtrA-type protease Ynm3/Nma111, and the ubiquitin ligase Ubr1. Various stresses stimulate ROQ1 transcription. The Roq1 protein is cleaved by Ynm3. Cleaved Roq1 interacts with Ubr1, transforming its substrate specificity. Altered substrate recognition by Ubr1 accelerates proteasomal degradation of misfolded as well as native proteins at the endoplasmic reticulum membrane and in the cytosol. We term this pathway stress-induced homeostatically regulated protein degradation (SHRED) and propose that it promotes physiological adaptation by reprogramming a key component of the quality control machinery.

    View details for DOI 10.1016/j.molcel.2018.04.027

    View details for Web of Science ID 000436640300008

    View details for PubMedID 29861160

  • A repeat protein links Rubisco to form the eukaryotic carbon-concentrating organelle PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Mackinder, L. C., Meyer, M. T., Mettler-Altmann, T., Chen, V. K., Mitchell, M. C., Caspari, O., Rosenzweig, E. S., Pallesen, L., Reeves, G., Itakura, A., Roth, R., Sommer, F., Geimer, S., Muehlhaus, T., Schroda, M., Goodenough, U., Stitt, M., Griffiths, H., Jonikas, M. C. 2016; 113 (21): 5958-5963


    Biological carbon fixation is a key step in the global carbon cycle that regulates the atmosphere's composition while producing the food we eat and the fuels we burn. Approximately one-third of global carbon fixation occurs in an overlooked algal organelle called the pyrenoid. The pyrenoid contains the CO2-fixing enzyme Rubisco and enhances carbon fixation by supplying Rubisco with a high concentration of CO2 Since the discovery of the pyrenoid more that 130 y ago, the molecular structure and biogenesis of this ecologically fundamental organelle have remained enigmatic. Here we use the model green alga Chlamydomonas reinhardtii to discover that a low-complexity repeat protein, Essential Pyrenoid Component 1 (EPYC1), links Rubisco to form the pyrenoid. We find that EPYC1 is of comparable abundance to Rubisco and colocalizes with Rubisco throughout the pyrenoid. We show that EPYC1 is essential for normal pyrenoid size, number, morphology, Rubisco content, and efficient carbon fixation at low CO2 We explain the central role of EPYC1 in pyrenoid biogenesis by the finding that EPYC1 binds Rubisco to form the pyrenoid matrix. We propose two models in which EPYC1's four repeats could produce the observed lattice arrangement of Rubisco in the Chlamydomonas pyrenoid. Our results suggest a surprisingly simple molecular mechanism for how Rubisco can be packaged to form the pyrenoid matrix, potentially explaining how Rubisco packaging into a pyrenoid could have evolved across a broad range of photosynthetic eukaryotes through convergent evolution. In addition, our findings represent a key step toward engineering a pyrenoid into crops to enhance their carbon fixation efficiency.

    View details for DOI 10.1073/pnas.1522866113

    View details for Web of Science ID 000376779900061

    View details for PubMedID 27166422

    View details for PubMedCentralID PMC4889370