Constance J. Jeffery, PhD

The genome projects yielded the sequences of tens of thousands of proteins. Elucidating the roles these proteins play in health and disease, and also how they can be used and/or modified for the development of novel therapeutics, biomaterials, biosensors, methods for energy production and methods for environmental remediation, will be aided by a better understanding of how a protein's amino acid sequence determines its structure and how structure determines function.  The Jeffery lab's research on protein structure and function combines methods from biophysics (X-ray crystallography), biochemistry, and bioinformatics to address questions such as: how does an enzyme bind to its substrate and convert it to product? how do two similar proteins perform different functions? how do some proteins perform multiple, unrelated ‘moonlighting functions’? how can we find small molecules that disrupt functions in proteins in cancer and tuberculosis and that can serve as drug leads? and how do mutations in proteins associated with autoimmune disease affect the proteins’ structures and functions?  In addition to research, Prof. Jeffery teaches upper level undergraduate biochemistry  (Bios352/Chem352) and a first-year graduate course in molecular biology and biochemistry (Bios524).

(1) Analysis of protein sequences and structures to elucidate the connections between sequence, structure and function. This information might help in the future in developing better methods to predict a protein's function(s) from its sequence or structure. Two current projects in this area include an analysis of ligand binding sites in protein crystal structures and a study of the sequences and structures of "moonlighting proteins". Many protein functions can be inferred from the known functions of homologous proteins, but determining protein functions is complicated by an increasing number of "moonlighting proteins", proteins that have more than one function where the multiple functions are not a result of splice variants, gene fusions, or multiple isoforms (Jeffery, C. J. Moonlighting Proteins. (1999) Trends in Biochemical Sciences. 24: 8-11). We have created a database of the known moonlighting proteins (The MoonProt Database at moonlightingproteins.org) and are performing an analysis of their sequences and structures. Knowing more about moonlighting proteins could help in predicting which additional proteins might also have a second function, which would be useful in determining the function(s) of the thousands of proteins identified through the genome projects and the functions of the "unknown" proteins whose structures were solved as part of the Protein Structure Initiative. In addition, since the ability of proteins to moonlight can complicate interpretation of the results of proteomics projects, identifying the roles of proteins in disease, and the selection of biomarkers, understanding which proteins moonlight can be important for both basic research and medicine.

(2) The development of novel approaches to increase the expression of transmembrane proteins for biochemical analysis and structure determination. Membrane proteins play key roles in health and disease and are the targets of the majority of pharmaceuticals in use today, but much less is known about their structures and mechanisms of function than for soluble proteins because of the challenges in their expression, purification, and structure determination. The goal of our new approaches is to alleviate the bottleneck in protein expression.

(3) In a previous project, we elucidated the reaction mechanism of a glycolytic enzyme that moonlights as a tumor cell motility factor in breast cancer cells: phosphoglucose isomerase/autocrine motility factor (PGI/AMF). By solving six structures of PGI/AMF with different ligands bound, we developed a model of the multistep catalytic mechanism for this multifunctional enzyme/growth factor.

(Complete list of publications on Google Scholar)

1. Jeffery CJ. (2019) An enzyme in the test tube, and a transcription factor in the cell: moonlighting proteins and cellular factors that affect their behavior.
   Protein Sci. 2019 May 14. doi: 10.1002/pro.3645.
2. Jeffery CJ. (2019) The demise of catalysis, but new functions arise: pseudoenzymes as the phoenixes of the protein world. Biochem Soc Trans. 2019 Feb 28;47(1):371-379. doi: 10.1042/BST20180473.
3. C. J. Jeffery (2019) Intracellular/surface moonlighting proteins that aid in the attachment of gut microbiota to the host. AIMS Microbiology 5(1): 77-86. doi: 10.3934/microbiol.2019.1.77
4. Chang Chen and C. J. Jeffery. (2019) Moonlighting Functions of Heat Shock Protein 90 In “Heat Shock Protein 90 in Human Diseases and Disorders” Prof. Dr. Alexzander A. A. Asea and Dr. Punit Kaur, editors, Volume 19 in the book series Heat Shock Proteins; Springer Nature Publishers (Dordrecht, Netherlands), In Press
5. Qingyu Chen, Ramona Britto, Ivan Erill, Constance Jeffery, Arthur Liberzon, Michele Magrane, Jun-ichi Onami, Marc Robinson-Rechavi, Jana Sponarova, Roxanne Yamashita, Justin Zobel, Karin Verspoor. (2019) Quality Matters: Biocuration experts on the impact of duplication and other data quality issues in biological databases. Genomics, Proteomics & Bioinformatics. In Press
6. C. J. Jeffery (2019) The use of proteomics studies in identifying moonlighting proteins in Functional Proteomics: Methods and Protocols eds. Xing Wang, and Mattrew Kuruc, Springer Science and Business Media, LLC, New York. 437-443.
7. C. J. Jeffery (2018) Intracellular proteins moonlighting as bacterial adhesion factors. AIMS Microbiology. 4(2): 362–376. DOI: 10.3934/microbiol.2018.2.362
8. Bhatt F, Patel V, Jeffery CJ. (2018) Open Conformation of the Escherichia coli Periplasmic Murein Tripeptide Binding Protein, MppA, at High Resolution. Biology (Basel). 7(2). pii: E30. doi: 10.3390/biology7020030. PMID: 29783769
9. Chang Chen, Shadi Zabad, Haipeng Liu, Wangfei Wang, C. J. Jeffery (2018) MoonProt 2.0: an expansion and update of the moonlighting proteins database.  Nucleic Acids Research, Volume 46, Issue D1, 4 January 2018, Pages D640–D644, https://doi.org/10.1093/nar/gkx1043
10. C. J. Jeffery. (2018) Protein moonlighting: What is it, and why is it important. Philosophical Transactions of the Royal Society B.  Jan 19;373(1738). pii: 20160523. doi: 10.1098/rstb.2016.0523. PMID:29203708
11. C. J. Jeffery.  (2017) Moonlighting Proteins – Nature’s Swiss Army Knives.  Science Progress. Nov 17;100(4):363-373. doi: 10.3184/003685017X15063357842574. PMID: 29113626
12. W. Wang and C. J. Jeffery. (2016) An Analysis of Surface Proteomics Results Reveals Novel Candidates for Intracellular/Surface Moonlighting Proteins in Bacteria. Molecular BIoSystems.  12(5):1420-31. doi: 10.1039/c5mb00550g. PMID: 26938107.
13. C. J. Jeffery.  (2016) Protein Species and Moonlighting Proteins: Very Small Changes in a Protein’s Covalent Structure Can Change its Biochemical Function. Journal of Proteomics. 134:19-24.doi: 10.1016/j.jprot.2015.10.003. PMID: 26455812.
14. C. J. Jeffery. (2016) Expression, Solubilization and Purification of Bacterial Membrane Proteins. Current Protocols in Protein Science. 83:29.15.1-29.15.15. doi: 10.1002/0471140864.ps2915s83 PMID: 26836409.
15. C. J. Jeffery. (2016) Expression, Solubilization and Purification of Bacterial Membrane Proteins. Current Protocols in Protein Science. 83:29.15.1-29.15.15. doi: 10.1002/0471140864.ps2915s83 PMID: 26836409.
16. C. J. Jeffery.  (2015) Why Study Moonlighting Proteins?  Frontiers in Genetics.  Research Topic on Moonlighting Proteins.  6:211. doi:10.3389/fgene.2015.00211.
17. Amblee, V. and C. J. Jeffery.  (2015) Physical Features of Intracellular Proteins that Moonlight on the Cell Surface.  PLOS One. 10(6):e0130575. doi: 10.1371/journal.pone.0130575. eCollection 2015. PMID: 26110848.
18. Mani, M. C. Chen, V. Amblee, H. Liu, T. Mathur, G. Zwicke, S. Zabad, B. Patel, J. Thakkar, and C. J. Jeffery.  (2015) Moonlighting Proteins Database (MoonProt): A database of proteins that are known to moonlight. Nucleic Acids Research. 43: D277–D282.
19. C. J. Jeffery.  (2015) Lung Cancer, Small Cell. in The SAGE Encyclopedia of Cancer and Society, Second Edition, editors Colditz, Graham A., Golson, J. Geoffrey. SAGE Publications, Inc. Thousand Oaks, California.  In Press.
20. C. J. Jeffery. (2014) An introduction to protein moonlighting.  Biochem Soc Trans. 42(6):1679-83. doi: 10.1042/BST20140226. PMID: 25399589.

PhD, University of California at Berkeley

BS, Massachusetts Institute of Technology