Caprin-1 binding to the critical stress granule protein G3BP1 is influenced by pH

May 10, 2023Open biology

Caprin-1’s interaction with the key stress granule protein G3BP1 changes with pH

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Abstract

The crystal structure of G3BP1-NTF2 in complex with a Caprin-1-derived motif reveals distinct binding interactions.

  • G3BP1 interacts with Caprin-1 and USP10, which may promote and inhibit stress granule formation, respectively.
  • Caprin-1 binds to a specific site on G3BP1-NTF2, distinct from the site used by USP10.
  • G3BP1-NTF2 exhibits reduced thermal stability at acidic pH, with USP10 stabilizing it more effectively than Caprin-1.
  • The G3BP1/USP10 complex shows increased resistance to acidic conditions compared to the G3BP1/Caprin-1 complex.
  • Cellular acidification of approximately 0.5 pH units relative to the cytosol was observed in human cells.
  • Higher binding affinity of a Caprin-1/FGDF chimera to G3BP1 was associated with reduced Caprin-1 levels and condensate sizes.

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