Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: A227
Charlotte Fare (University of Pennsylvania), Vladislav Korobeynikov (Columbia University ), Kevin Rhine (Johns Hopkins University), Joey Yoniles (Johns Hopkins University), Sua Myong (Johns Hopkins University), Neil Shneider (Columbia University ), James Shorter (University of Pennsylvania)
Karyopherin-β2 (Kapβ2) is a nuclear import receptor (NIR) that localizes proteins bearing a proline-tyrosine nuclear localization signal (PY-NLS) to the nucleus, including the RNA-binding protein (RBP) FUS. Recent work has demonstrated that NIRs can chaperone RBPs in vitro and in cells, preventing and reversing their self-assembly and aggregation. However, when the PY-NLS is mutated, Kapβ2 no longer efficiently chaperones its cargo. Here, we focus on the case of FUSP525L, an RBP NLS mutant associated with a highly aggressive form of juvenile ALS. Using a structural approach, we have engineered Kapβ2 to recognize mutant FUS and demonstrate improved chaperone activity in vitro, in human cells, and in mice.
Support or Funding Information
C.M.F. is supported by NIH grant nos. T32GM008275 and F31NS111870.
