Jeanine Amacher , PhD
Associate Professor of Biochemistry
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.
†WWU MS student; *WWU undergraduate student
*Johnson DA, *Piper IM, †Vogel BA, †Jackson SN, *Svendsen JE, *Kodama HM, *Lee DE, *Lindblom KM, McCarty J, Antos JM, Amacher JF. Structures of Streptococcus pyogenes class A sortase in complex with substrate and product mimics provide key details of target recognition. J Biol Chem. (2022) 298(10):102446.
*Gao M, *Johnson DA, *Piper IM, *Kodama HM, *Svendsen JE, *Tahti E, *Vogel B, Antos JM, Amacher JF. Structural and biochemical analyses of selectivity determinants in chimeric Streptococcus Class A sortase enzymes. Protein Science. (2022) 31(3):701-715.
†Wofford HA, *Myers-Dean J, *Vogel B, *Alamo KAE, *Longshore-Neate F, Jagodzinski F, Amacher JF. (2021) Domain Analysis and Motif Matcher (DAMM): A program to predict selectivity determinants in Monosiga brevicollis PDZ domains using human PDZ data. Molecules. (2021) 26(19):6034.
*Piper IM, †Struyvenberg SA, *Valgardson JD, *Johnson DA, *Gao M, *Johnston K, *Svendsen JE, *Kodama HM, Hvorecny KL, Antos JM, Amacher JF. (2021) Sequence variation in the b7-b8 loop of bacterial Class A sortase enzymes alters substrate selectivity. J Biol Chem. (2021) 297(2):100981.
*Gao M, *Mackley IGP, Mesbahi-Vasey S, †Bamonte HA, †Struyvenberg SA, *Landolt L, *Pederson NJ, *Williams LI, Bahl CD, Brooks 3rd L, Amacher JF. (2020) Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis. Protein Science. 29(11):2226-44.
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 JF. MotifAnalyzer-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 Sci. 2018. 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.