The Role of Linker Length and Composition in Actin Binding and Bundling by Palladin.

ABSTRACT: Interdomain linkers in multidomain proteins influence spatial arrangement, flexibility, and cooperative binding, yet their functional roles remain underexplored. Palladin, an actin scaffold protein essential for cytoskeletal organization, contains tandem immunoglobulin domains (Ig3-4) separated by an unusually long (~41-residue), arginine-rich, intrinsically disordered linker. While Ig3 mediates direct F-actin binding, the adjacent Ig4 domain and linker enhance binding and bundling, suggesting active roles beyond passive connection. Using targeted mutagenesis, actin co-sedimentation, bundling assays, and SAXS, we show that linker length, charge, and residue patterning are critical for activity. Shortening or replacing the 41-residue linker with the native Ig4-Ig5 linker reduced binding and

SUBMITTER: Sargent RA 

PROVIDER: S-EPMC12637626 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature