Amy Weeks

@amyweeks.bsky.social

1615 Followers 317 Following

Asst Prof @ UW-Madison Biochemistry. Protein Engineering, Chemical Biology, Proteomics, Proteases, Enzymology.

A handmade poster that says "We are all in this together" with a DNA double helix in the center.
A crystal structure of the OspF homolog SpvC bound to a substrate peptide. Plots of % sites beta-eliminated for pThr and pSer with several OspF variants.
OspF is a pThr lyase from Shigella flexneri that targets MAPKs in innate immune signaling. We profiled OspF activity on PhosPropels and found that its catalytic domain has an intrinsic preference for the the MAPK activation loop motif pThr-X-pTyr.
The Legionella pneumophila phosphatase WipB targets the lysosomal nutrient sensing machinery. WipB disfavors substrates with Pro at +1 and phosphosites flanked by acidic residues.
Workflow for PhosPropel-based profiling of phosphoerasers. Cells are lysed, protein is digested, and phosphopeptides are enriched to generated a phosphoproteome-derived peptide library (PhosPropel). The PhosPropel can then be treated with a phosphoeraser enzyme and analyzed using LC-MS/MS to profile enzyme specificity.
Position-specific frequency matrices can be used to calculate z-scores comparing enzyme-treated and control samples. The z-scores are plotted as heatmaps that represent an enzyme specificity profile.
OspF is a pThr lyase from Shigella flexneri that dampens innate immune signaling. We treated PhosPropels with OspF and found that this enzyme has intrinsic specificity for the pThr-X-pTyr motif of MAPK activation loops independent of an N-terminal MAPK docking motif.
WipB is a Ser/Thr phosphatase from Legionella pneumophila that targets lysosomal nutrient sensing machinery. PhosPropel analysis revealed that WipB disfavors substrates with Pro at +1 and phosphosites flanked by acidic residues.
Workflow for phosphoeraser specificity profiling. Cells are lysed, protein is digested, phosphopeptides are enriched, the phosphopeptide library is treated with an eraser enzyme, and phosphosites are analyzed by LC-MS/MS
Debashrito Deb holding up his poster award at the 2025 Bioorganic GRC
A Festivus Pole
Members of the Weeks lab posing for a photo