Jeanine Amacher , PhD

Associate Professor of Biochemistry · she/her

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 specificity 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 specifcity 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 (e.g., 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

†WWU MS student; *WWU undergraduate student

  • *Longshore-Neate F, *Ceravolo C, *Masuga C, *Tahti EF, **Blount JM, †Smith SN, Amacher JF. The conformation of the nSrc specificity-determining loops in the Src and Abl SH3 domains are modulated by a WX conserved sequence motif. bioRxiv and In Press. (2024) https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1487276/abstract

  • †Jackson SN, †Lee DE, **Blount JM, †Croney KA, *Ibershof JW, *Ceravolo C, *Brown K, †Whitham KM, McCarty J, Antos JM, Amacher JF. Biochemical characterization of Bacillus anthracis sortase B: Use in sortase-mediated ligation and substrate recognition dependent on residues beyond the canonical pentapeptide binding motif for sortase enzymes. bioRxiv and In Revision. 2024. doi.org/10.1101/2024.05.07.593036. **Jadon JM was a Cottrell Postbac scholar.

  • *Kodama HM, *Lindblom KM, †Walkenhauer EG, Antos JM, Amacher JF. Amino acid variability at W194 of Staphylococcus aureus sortase A alters nucleophile specificity. Protein Sci. (2024) 33(12):e5212.

  • Berger RF, Amacher JF. Implementation of professional development initiatives in chemistry at a regional public university. ACS Symposium Series. doi: 10.1021/bk-2024-1470. [Invited chapter]

  • Amacher JF, Antos JM. Sortases: structure, mechanism, and implications for protein engineering. Trends Biochem Sci. (2024) 49(7):596-610. [Invited review]

  • †Vogel BA, **Blount JM, *Kodama HM, *Goodwin-Rice NJ, Andaluz DJ, †Jackson SN, Antos JM, Amacher JF. A unique binding mode of P1’ Leu-containing target sequences for Streptococcus pyogenes sortase A results in alternative cleavage. RSC Chem Biol. (2023) 5(1):30-40. **Jadon JM was a Cottrell Postbac scholar.

  • *Tahti EF, *Blount JM, †Jackson SN, *Gao M, Gill NP, †Smith SN, *Pederson NJ, *Rumph SN, *Stuyvenberg SA, *Mackley IGP, Madden DR, Amacher JF. Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets. Protein Sci. (2023) 32(4):e4611.

  • Godse S, Sapar T, Amacher JF. Engaging high school students in structure-function studies of bacterial sortase enzymes and inhibitors: A comprehensive computational experimental pipeline. Biochem Mol Biol Educ. (2023) 51(6):606-615. *Godse S and Sapar T were high school students.

  • *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.

  • For a full list of our publications please see our lab website or https://www.ncbi.nlm.nih.gov/myncbi/1LoFccQwL3mkd/bibliography/public/