Membrane-dependent assembly of Bruton's tyrosine kinase mediated by the Proline-rich region and SH3 domain.

ABSTRACT: Cellular membranes provide a unique platform for interactions that drive emergent behaviors in protein dynamics and cellular signaling, distinct from those observed in solution. We investigated the proline-rich region (PRR) and Src Homology 3 (SH3) domains of Bruton's tyrosine kinase (Btk) and its phase separation driven by the weak interactions of regulatory domains at membrane surfaces. Using supported lipid bilayers (SLBs) and giant unilamellar vesicles (GUVs), we demonstrate that membrane localization amplifies weak PRR-SH3 interactions, enabling the formation of higher-order assemblies and phase-separated condensates. These assemblies, previously undescribed by solution-state studies, are supported by reductions in the lateral diffusion of membrane-bound Btk molecules and the stabiliz

SUBMITTER: Fenton AD 

PROVIDER: S-EPMC12268371 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature