Jeanine Amacher , PhD

Assistant Professor of Biochemistry

Research Interests

Our research group is broadly interested in peptide-binding domains and how only a small number of amino acids are recognized in a given interaction. Specifically, we are focused on a number of these types of domains, including bacterial sortases, and scaffolding PDZ, SH2, and SH3 domains. For example, the PDZ domain is important in signaling and trafficking pathways in the cell. There are over 200 PDZ domains in the human proteome, making it the largest family of peptide-binding domains. Defined motifs include only a couple of positions along the peptide-binding cleft, and do not accurately define the overlapping yet distinct preferences among family members. Our research group is working to understand the selectivity determinants of PDZ domains throughout evolution. We use biochemistry and structural biology to investigate PDZ domains from extant species, as well as PDZ domains in choanoflagellates. We are also interested in the selectivity determinants of other peptide-binding domains, particularly those that have structurally-conserved specificity-determining loops. Our work in bacterial sortases, for example, investigating the role of the beta7-beta8 loop in selectivity and activity has revealed that varying the sequence of this loop has profound impacts on protein function. In this project, we are studying chimeric enzymes of Class A sortases from Streptococcus families (i.e., S. pneumoniae, S. agalactiae, and S. pyogenes) and Staphylococcus aureus. 

Educational & Professional Experience

  • B.S. Physics, University of Oregon, 2007.
  • Ph.D. Biochemistry, Geisel School of Medicine at Dartmouth, 2014.
  • Postdoctoral Fellow, University of California, Berkeley, 2014-2017.
  • Jane Coffin Childs Memorial Fund for Medical Research Postdoctoral Fellow, University of California, Berkeley, 2015-2017.

Recent Publications

  • Gao M, Mackley IGP, Mesbahi-Vasey S, Bamonte HA, Struyvenberg SA, Landolt L, Pederson NJ, Williams LI, Bahl CD, Brooks 3rd L, Amacher JF. Structural characterization and computational analysis of PDZ domains in Monosiga brevicollisProtein Sci. 2020. doi:10.1002/pro.3947. In press.

  • Amacher JF, Brooks 3rd L, Hampton TH, Madden DR. Specificity in PDZ-peptide interaction networks: Computational analysis and review. J Struct Biol X. 2020. 4:100022.

  • Valgardson J*, Cosbey R*, Houser P*, Rupp M, Van Bronkhorst R, Lee M, Jagodzinski F, Amacher JFMotifAnalyzer-PDZ: A computational program to investigate the evolution of PDZ-binding target specificity. Protein Sci. 2019. 28(12):2127-43. *These authors contributed equally to this study.

  • Shah NH, Amacher JF, Nocka L, Kuriyan J. The Src module: an ancient scaffold in the evolution of cytoplasmic tyrosine kinases. Crit Rev Biochem Mol Biol. 2018. Sep 5: 1-29. Review.

  • Amacher JF, Hobbs HT, Cantor AC, Shah L, Rivero MJ, Mulchand SA, Kuriyan J. Phosphorylation control of the ubiquitin ligase Cbl is conserved in choanoflagellates. Protein Sci2018. 27(5): 923-32.

  • Courtney AH, Amacher JF, Kadlecek TA, Mollenauer MN, Au-Yeung BB, Kuriyan J, Weiss A. A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45. Mol Cell. 2017. 67(3):498-511

  • Amacher JF, Zhong F, Lisi GP, Zhu MQ, Alden SL, Hoke KR, Madden DR, Pletneva EV. A Compact Structure of Cytochrome c Trapped in a Lysine-Ligated State: Loop Refolding and Functional Implications of a Conformational Switch. J Am Chem Soc. 2015. 137(26):8435-49.

  • Qian Z, Xu X, Amacher JF, Madden DR, Cormet-Boyaka E, Pei D. Intracellular Delivery of Peptidyl Ligands by Reversible Cyclization: Discovery of a PDZ Domain Inhibitor that Rescues CFTR Activity. Angew Chem. 2015. 54(20):5874-8.

  • Amacher JF, Zhao R, Spaller MR, Madden DR. Chemically modified peptide scaffolds target the CFTR-associated ligand PDZ domain. PLoS One. 2014. 9(8):e103650.

  • Amacher JF, Cushing PR, Brooks L 3rd, Boisguerin P, Madden DR. Stereochemical preferences modulate affinity and selectivity among five PDZ domains that bind CFTR: comparative structural and sequence analyses. Structure. 2014. 22(1):82-93.

  • Amacher JF, Cushing PR, Bahl CD, Beck T, Madden DR. Stereochemical determinants of C-terminal specificity in PDZ peptide-binding domains: a novel contribution of the carboxylate-binding loop. J Biol Chem. 2013. 288(7):5114-26.